Xiao, Cheng, Nashmi, Raad, McKinney, Sheri, Cai, Haijiang, McIntosh, J. Michael, Lester, Henry A.
These electrophysiological experiments, in slices and intact animals, study the effects of in vivo chronic exposure to nicotine on functional α4β2* nAChRs in the nigrostriatal dopaminergic (DA)...
Pantoja, Rigo, Srinivasan, Rahul, Kadambi, Sindhuja, Mackey, Elisha D. W., Tzlil, Shelly, Moss, Fraser J., ...
[No abstract]
Srinivasan, Rahul, Pantoja, Rigo, Kadambi, Sindhuja, Mackey, Elisha D. W., Tzlil, Shelly, Moss, Fraser J., ...
[Poster abstract]
Breining, Scott R., Bencherif, Merouane, Grady, Sharon R., Whiteaker, Paul, Marks, Michael J., Wageman, Charles R., ...
Direct comparison of pyridine versus pyrimidine substituents on a small but diverse set of ligands indicates that the pyrimidine substitution has the potential to enhance affinity and/or functional...
Torrice, Michael M., Bower, Kiowa S., Lester, Henry A., Dougherty, Dennis A.
We describe a general application of the nonsense suppression methodology for unnatural amino acid incorporation to probe drug–receptor interactions in functional G protein-coupled receptors...
Gleitsman, Kristin R., Lester, Henry A., Dougherty, Dennis A.
Long-range communication is essential for the function of members of the Cys-loop family of neurotransmitter-gated ion channels. The involvement of the peptide backbone in binding-induced...
Son, Cagdas D., Moss, Fraser J., Cohen, Bruce N., Lester, Henry A.
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is linked with high penetrance to several distinct nicotinic receptor (nAChR) mutations. We studied (α4)_3(2β)_2 versus (α4)_2(β2)_3...
Long-Range Coupling in an Allosteric Receptor Revealed by Mutant Cycle Analysis (2009)
Gleitsman, Kristin R., Shanata, Jai A. P., Frazier, Shawnalea J., Lester, Henry A., Dougherty, Dennis A.
The functional coupling of residues that are far apart in space is the quintessential property of allosteric proteins. For example, in Cys-loop receptors, the gating of an intrinsic ion channel is...
Imoukhuede, P. I., Moss, Fraser J., Michael, Darren J., Chow, Robert H., Lester, Henry A.
A high density of neurotransmitter transporters on axons and presynaptic boutons is required for the efficient clearance of neurotransmitters from the synapse. Therefore, regulators of transporter...
Bohland, Jason, Wu, Caizhi, Barbas, Helen, Bokil, Hemant, Bota, Mihail, Breiter, Hans C., ...
In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is critical, however, for both basic and clinical research into brain function....
Nicotine binding to brain receptors requires a strong cation–π interaction (2009)
Xiu, Xinan, Puskar, Nyssa L., Shanata, Jai A. P., Lester, Henry A., Dougherty, Dennis A.
Nicotine addiction begins with high-affinity binding of nicotine to acetylcholine (ACh) receptors in the brain. The end result is over 4,000,000 smoking-related deaths annually worldwide and the...
Lester, Henry A., Xiao, Cheng, Srinivasan, Rahul, Son, Cagdas D., Miwa, Julie, Pantoja, Rigo, ...
The acronym SePhaChARNS, for “selective pharmacological chaperoning of acetylcholine receptor number and stoichiometry,” is introduced. We hypothesize that SePhaChARNS underlies classical...
Bohland, Jason W., Wu, Caizhi, Barbas, Helen, Bokil, Hemant, Bota, Mihail, Breiter, Hans C., ...
In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function....
Pantoja, Rigo, Rodriguez, Erik A., Dibas, Mohammed I., Dougherty, Dennis A., Lester, Henry A.
We report on the first, to our knowledge, successful detection of a fluorescent unnatural amino acid (fUAA), Lys(BODIPYFL), incorporated into a membrane protein (the muscle nicotinic acetylcholine...
Pantoja, Rigo, Rodriguez, Erik A., Dibas, Mohammed I., Dougherty, Dennis A., Lester, Henry A.
We report on the first, to our knowledge, successful detection of a fluorescent unnatural amino acid (fUAA), Lys(BODIPYFL), incorporated into a membrane protein (the muscle nicotinic acetylcholine...
Gleitsman, Kristin Rule, Kedrowski, Sean M. A., Lester, Henry A., Dougherty, Dennis A.
The muscle nicotinic acetylcholine receptor (nAChR) is a large, allosteric, ligand-gated ion channel with the subunit composition α2βγδ. Though much is now known about the structure of the...
Pless, Stephan A., Millen, Kat S., Hanek, Ariele P., Lynch, Joseph W., Lester, Henry A., Lummis, Sarah C. R., ...
Cys-loop receptor binding sites characteristically contain many aromatic amino acids. In nicotinic ACh and 5-HT3 receptors, a Trp residue forms a cation-{pi} interaction with the agonist, whereas in...
Drenan, Ryan M., Grady, Sharon R., Whiteaker, Paul, McClure-Begley, Tristan, McKinney, Sheri, Miwa, Julie M., ...
α6-containing (α6*) nicotinic ACh receptors (nAChRs) are selectively expressed in dopamine (DA) neurons and participate in cholinergic transmission. We generated and studied mice with...
Hanek, Ariele P., Lester, Henry A., Dougherty, Dennis A.
Understanding the gating mechanism of the nicotinic acetylcholine receptor (nAChR) and similar channels constitutes a significant challenge in chemical neurobiology. In the present work, we use a...
Demonstration of functional α4-containing nicotinic receptors in the medial habenula (2008)
Fonck, Carlos, Nashmi, Raad, Salas, Ramiro, Zhou, Chunyi, Huang, Qi, De Biasi, Mariella, ...
The medial habenula (MHb) exhibits exceptionally high levels of nicotinic acetylcholine receptors (nAChRs), but it remains unclear whether all expressed nAChR subunit mRNAs are translated to form...
Shao, Xuesi M, Tan, Wenbin, Xiu, Joanne, Puskar, Nyssa, Fonck, Carlos, Lester, Henry A, ...
Acetylcholine and nicotine can modulate respiratory patterns by acting on nicotinic acetylcholine receptors (nAChRs) in the preBotzinger complex (preBotC). To further explore the molecular...
Pless, Stephan A., Millen, Kat S., Hanek, Ariele P., Lynch, Joseph W., Lester, Henry A., Lummis, Sarah C. R., ...
Pless, Stephan A., Dibas, Mohammed I., Lester, Henry A., Lynch, Joseph W.
Models describing the structural changes mediating cys-loop receptor activation generally give little attention to the possibility that different agonists may promote activation via distinct M2...
Allosteric Control of Gating and Kinetics at P2X (2007)
Receptor Channels Baljit, Baljit S. Khakh, William R. Proctor, Thomas V. Dunwiddie, Cesar Labarca, Henry A. Lester
urprisingly, IVM produced no significant effect on the fast ATP-evoked inward currents in either type of neuron, despite the fact that IVM modulated P2X 4 channels heterologously expressed in...
Mapping Disulfide Connectivity Using Backbone Ester Hydrolysis (2007)
Pamela England Henry, Henry A. Lester, Dennis A. Dougherty
: The site-specific incorporation of R-hydroxy acids into proteins using nonsense suppression can provide a powerful probe of protein structure and function. The resulting backbone ester may be...
Dynamic Selectivity Filters Review in Ion Channels (2007)
Functioning For Brief, Baljit S. Khakh, Henry A. Lester
otein is that some ion channels can change their ion selectivity extracellular, and this loop has ten conserved cysteines such that normally impermeant ions do in fact permeate (not all shown in...
Cyclic nucleotide-gated channels are nonselective cation channels activated by intracellular cAMP and/or cGMP. It is not known how the binding of agonists opens the channel, or how the presumed four...
Jun Li And, Jun Li, Henry A. Lester
The ligand-binding domains of cyclic nucleotide-gated (CNG) channels show sequence homology to corresponding region(s) of the Escherichia coli catabolite gene-activator protein (CAP) and to the...
Brain Gaba, Transporter Gat, Michael W. Quick, Janis L. Corey, Norman Davidson, Henry A. Lester
this report, we use Xenopus oocytes to permit high-level expression of wild-type and mutant transporters, to identify trafficking proteins affecting GAT1 expression, and to allow for detailed phys-...
Yanhe Tong, Gabriel S. Br, Ming Li, George Shapovalov, Eric Slimko, Andreas Karschin, ...
abstract Tyrosine side chains participate in several distinct signaling pathways, including phosphorylation and membrane trafficking. A nonsense suppression procedure was used to incorporate a caged...
Joshua A. Maurer, Donald E. Elmore, Henry A. Lester, Dennis A. Dougherty
was used to develop an optimal alignment for Escherichia coli and Mycobacterium tuberculosis MscL and to place these homologues into sequence subfamilies. By using this alignment, previously...
Probing the Role of a Conserved M1 Proline Residue in (2007)
Hong Dang, Pamela M. England, S. Sarah Farivar, Dennis A. Dougherty, Henry A. Lester
A conserved proline residue is found in the first transmembrane domain (M1) of every subunit in the ligand-gated ion channel superfamily. The position of this proline between the N-terminal...
Abraham Kovoor, Ching-kang Chen, Wei He, Theodore G. Wensel, Melvin I, Henry A. Lester
SUMMARY Regulators of G protein signaling (RGS) stimulate the GTPase activity of G protein Gα subunits and probably play additional roles. Some RGS proteins contain a Gγ subunit-like (GGL) domain...
Rodriguez, Erik A., Lester, Henry A., Dougherty, Dennis A.
The incorporation of unnatural amino acids site-specifically is a valuable technique for structure–function studies, incorporation of biophysical probes, and determining protein–protein...
Rodriguez, Erik A., Lester, Henry A., Dougherty, Dennis A.
The incorporation of unnatural amino acids into proteins is a valuable tool for addition of biophysical probes, bio-orthogonal functionalities, and photoreactive cross-linking agents, although these...
Wang, Jinti, Lester, Henry A., Dougherty, Dennis A.
{gamma}-Aminobutyric acid type A (GABAA) receptors are members of the Cys-loop superfamily of ligand-gated ion channels. Upon agonist binding, the receptor undergoes a structural transition from the...
Whyte, Douglas, Cahir, Elizabeth, Lester, Henry A, Grady, Sharon R, Marks, Michael J, ...
We generated a mouse line harboring an autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE) mutation: the alpha 4 nicotinic receptor S248F knock-in strain. In this mouse, modest nicotine doses...
Rodent Aβ Modulates the Solubility and Distribution of Amyloid Deposits in Transgenic Mice (2007)
Jankowsky, Joanna L., Younkin, Linda H., Gonzales, Victoria, Fadale, Daniel J., Slunt, Hilda H., Lester, Henry A., ...
The amino acid sequence of amyloid precursor protein (APP) is highly conserved, and age-related Abeta aggregates have been described in a variety of vertebrate animals, with the notable exception of...
Ahern, Christopher A., Eastwood, Amy L., Lester, Henry A., Dougherty, Dennis A., Horn, Richard
Open-channel blockers such as tetraethylammonium (TEA) have a long history as probes of the permeation pathway of ion channels. High affinity blockade by extracellular TEA requires the presence of an...
Rodriguez, Erik A., Lester, Henry A., Dougherty, Dennis A.
Site-specific incorporation of unnatural amino acids (UAAs) into proteins is a valuable tool for studying structure–function relationships, incorporating biophysical probes, and elucidating...
Xiu, Xinan, Hanek, Ariele P., Wang, Jinti, Lester, Henry A., Dougherty, Dennis A.
In the Cys loop superfamily of ligand-gated ion channels, a global conformational change, initiated by agonist binding, results in channel opening and the passage of ions across the cell membrane....
Jankowsky, Joanna L., Slunt, Hilda H., Gonzales, Victoria, Savonenko, Alena V., Wen, Jason C., Jenkins, Nancy A., ...
Background: The proteases (secretases) that cleave amyloid-β (Aβ) peptide from the amyloid precursor protein (APP) have been the focus of considerable investigation in the development of treatments...
Joanna L. Jankowsky, Hilda H. Slunt, Victoria Gonzales, Alena V. Savonenko, Jason C. Wen, Nancy A. Jenkins, ...
In a transgenic mouse that overexpressed amyloid beta, turning off production via a tetracycline sensitive switch did not decrease the number of amyloid plaques present
Joanna L. Jankowsky, Hilda H. Slunt, Victoria Gonzales, Alena V. Savonenko, Jason C. Wen, Nancy A. Jenkins, ...
Background The proteases (secretases) that cleave amyloid-β (Aβ) peptide from the amyloid precursor protein (APP) have been the focus of considerable investigation in the development of treatments...
Gating Transitions in Bacterial Ion Channels Measured at 3 µs Resolution (2004)
Shapalov, George, Lester, Henry A.
Ion channels of high conductance (>200 pS) are widespread among prokaryotes and eukaryotes. Two examples, the Escherichia coli mechanosensitive ion channels Ec-MscS and Ec-MscL, pass currents of...
Dahan, David S., Dibas, Mohammed I., Petersson, E. James, Auyeung, Vincent C., Chanda, Baron, Bezanilla, Francisco, ...
To study conformational transitions at the muscle nicotinic acetylcholine (ACh) receptor (nAChR), a rhodamine fluorophore was tethered to a Cys side chain introduced at the beta-19' position in the...
Clayton, Daniel, Shapovalov, George, Maurer, Joshua A., Dougherty, Dennis A., Lester, Henry A., Kochendoerfer, Gerd G.
Total chemical protein synthesis was used to generate multimilligram quantities of the mechanosensitive channel of large conductance from Escherichia coli (Ec-MscL) and Mycobacterium tuberculosis...
Leite, John F., Blanton, Michael P., Shahgholi, Mona, Dougherty, Dennis A., Lester, Henry A.
We characterized the differential accessibility of the nicotinic acetylcholine receptor all subunit in the open, closed, and desensitized states by using electrophysiology-coordinated photolabeling...
Jensen, Kimmo, Chiu, Chih-Sung, Sokolova, Irina, Lester, Henry A, Mody, Istvab
Abstract is not available
Gutman,George A., Chandy,K.George, Adelman,John P., Aiyar,Jayashree, Bayliss,Douglas A., Clapham,David E., ...
This summary article presents an overview of the molecular relationships among the voltage-gated potassium channels and a standard nomenclature for them, which is derived from the IUPHAR Compendium...
Gutman, George A., Chandy, K.George, Adelman, John P., Aiyar, Jayashree, Bayliss, Douglas A., Clapham, David E., ...
This summary article presents an overview of the molecular relationships among the voltage-gated potassium channels and a standard nomenclature for them, which is derived from the IUPHAR Compendium...
Gutman, George A., Chandy, K. George, Adelman, John P., Aiyar, Jayashree, Bayliss, Douglas A., Clapham, David E., ...
This summary article presents an overview of the molecular relationships among the voltage-gated potassium channels and a standard nomenclature for them, which is derived from the IUPHAR Compendium...
Control of P2X2 Channel Permeability by the Cytosolic Domain (2002)
Eickhorst, Angela N., Berson, Amy, Cockayne, Debra, Lester, Henry A., Khahk, Baljit S.
ATP-gated P2X channels are the simplest of the three families of transmitter-gated ion channels. Some P2X channels display a time- and activation-dependent change in permeability as they undergo the...
Yu, Tzu-ping, McKinney, Sheri, Lester, Henry A., Davidson, Norman
cAMP induces a protein-synthesis-dependent late phase of longterm potentiation (LTP) at CA3-CA1 synapses in acute hippocampal slices. Herein we report cAMP-mediated LTP and long-term depression (LTD)...
Khakh, Baljit S., Smith, W. Bryan, Chiu, Chi-Sung, Ju, Donghong, Davidson, Norman, Lester, Henry A.
ATP-gated P2X(2) receptors are widely expressed in neurons, but the cellular effects of receptor activation are unclear. We engineered functional green fluorescent protein (GFP)-tagged P2X(2)...
Labarca, Cesar, Schwarz, Johannes, Deshpande, Purnima, Schwarz, Sigrid, Nowak, Mark W., Fonck, Carlos, ...
Knock-in mice were generated that harbored a leucine-to-serine mutation in the alpha4 nicotinic receptor near the gate in the channel pore. Mice with intact expression of this hypersensitive receptor...
Tong, Yanhe, Brandt, Gabriel S., Li, Ming, Shapovalov, George, Slimko, Eric, Karschin, Andreas, ...
Tyrosine side chains participate in several distinct signaling pathways, including phosphorylation and membrane trafficking. A nonsense suppression procedure was used to incorporate a caged tyrosine...
Chiu, Chi-Sung, Ross, Linda S., Cohen, Bruce N., Lester, Henry A., Gill, Sarjeet S.
We cloned the inebriated homologue MasIne from Manduca sexta and expressed it in Xenopus laevis oocytes. MasIne is homologous to neurotransmitter transporters but no transport was observed with a...
Maurer, Joshua A., Elmore, Donald E., Lester, Henry A., Dougherty, Dennis A.
Sequence analysis of 35 putative MscL homologues was used to develop an optimal alignment for Escherichia coli and Mycobacterium tuberculosis MscL and to place these homologues into sequence...
Li, Ming, Farley, Robert A., Lester, Henry A.
The rat {gamma}-aminobutyric acid transporter GAT1 expressed in Xenopus oocytes was labeled at Cys74, and at one or more other sites, by tetramethylrhodamine-5-maleimide, without significantly...
Gain of function mutants: Ion channels and G protein-coupled receptors (2000)
Lester, Henry A., Karschin, Andreas
Many ion channels and receptors display striking phenotypes for gain-of-function mutations but milder phenotypes for null mutations. Gain of molecular function can have several mechanistic bases:...
Kovoor, Abraham, Chen, Ching-Kang, He, Wei, Wensel, Theodore G., Simon, Melvin I., Lester, Henry A.
Regulators of G protein signaling (RGS) stimulate the GTPase activity of G protein Galpha subunits and probably play additional roles. Some RGS proteins contain a Ggamma subunit-like (GGL) domain,...
Paulo Kofuji, Paul Ceelen, Kathleen R. Zahs, Leslie W. Surbeck, Henry A. Lester, Eric A. Newman
The inwardly rectifying potassium channel Kir4.1 has been suggested to underlie the principal K � conductance of mammalian Müller cells and to participate in the generation of field potentials and...
Ming Li, Robert A. Farley, Henry A. Lester
acid transporter GAT1 expressed in Xenopus oocytes was labeled at Cys74, and at one or more other sites, by tetramethylrhodamine-5-maleimide, without significantly altering GAT1 function....
McPhee, Jancy C., Dang, Yan L., Davidson, Norman, Lester, Henry A.
Heteromultimeric G protein-activated inward rectifier K+ (GIRK) channels, abundant in heart and brain, help to determine the cellular membrane potential as well as the frequency and duration of...
In the study of membrane-bound receptor, channel, and transporter proteins, classical pharmacology has defined highly specific agonists and antagonists; and quantitative structure-activity studies...
Zhong, Wenge, Gallivan, Justin P., Zhang, Yinong, Li, Lintong, Lester, Henry A., Dougherty, Dennis A.
The nicotinic acetylcholine receptor is the prototype ligand-gated ion channel. A number of aromatic amino acids have been identified as contributing to the agonist binding site, suggesting that...
Li, Yong-Xin, Xu, Youfeng, Ju, Donghong, Lester, Henry A., Davidson, Norman, Schuman, Erin M.
We have developed a method to analyze the relative contributions of pre- and postsynaptic actions of a particular gene product in neurons in culture and potentially in slices using...
New Views of Multi-Ion Channels (1998)
Lester, Henry A., Dougherty, Dennis A.
Thus, most site-directed mutagenesis data render it untenable to consider that two or more roughly equivalent high affinity sites govern selectivity in multi-ion pores. The papers by Dang and...
Scott K. Silverman, Henry A. Lester, Dennis A. Dougherty
We have investigated aspects of ion selectivity in K # channels by functional expression of wild-type and mutant heteromultimeric G protein-coupled inward-rectifier K # (GIRK) channels in Xenopus...
Yong-xin Li, Yinong Zhang, Henry A. Lester, Erin M. Schuman, Norman Davidson
> 2# ] o ). Fura-2 recordings showed that BDNF elicited an increase in intracellular calcium concentration ([Ca 2# ] c ). This effect was dependent on [Ca 2# ] o ; it was blocked by K252a and by...
Yongwei Cao, Ming Li, Sela Mager, Henry A. Lester
this paper (see Figs. 6, 7). TM, Transmembrane. B, Summary of the membrane topology shown in A. C, Alignments for 19 transporters, including #44 residues in the putative extracellular region studied...
Bjorkman, Pamela J., Dougherty, Dennis A., Lester, Henry A.
To provide material suitable for structural studies of the nicotinic acetylcholine receptor, we have expressed and purified the NH2-terminal extracellular domain of the mouse muscle alpha subunit....
Site-specific, photochemical proteolysis applied to ion channels in vivo (1997)
England, Pamela M., Lester, Henry A., Davidson, Norman, Dougherty, Dennis A.
A method for site-specific, nitrobenzyl-induced photochemical proteolysis of diverse proteins expressed in living cells has been developed based on the chemistry of the unnatural amino acid...
Doupnik, Craig A., Davidson, Norman, Lester, Henry A., Kofuji, Paulo
G protein gated inward rectifier K+ (GIRK) channels mediate hyperpolarizing postsynaptic potentials in the nervous system and in the heart during activation of G alpha(i/o) coupled receptors. In...
Ehrengruber, Markus U., Doupnik, Craig A., Xu, Youfeng, Garvey, Justine, Jasek, Mark C., Lester, Henry A., ...
G protein-gated inward rectifier K+ channel subunits 1-4(GIRK1-4) have been cloned from neuronal and atrial tissue and function as heterotetramers. To examine the inhibition of neuronal excitation by...
Li, Jun, Zagotta, William N., Lester, Henry A.
Most working proteins, including metabolic enzymes, transcription regulators, and membrane receptors, transporters, and ion channels, share the property of allosteric coupling. The term 'allosteric'...
Permeation and pH Regulation at a Mammalian Serotonin Transporter (1997)
Yongwei Cao Sela, Yongwei Cao, Sela Mager, Henry A. Lester
-function models that explain permeation properties of neurotransmitter transporters. Key words: protons; sodium; 5-HT; serotonin; SERT; Xenopus oocyte Neurotransmitter transporters play a key role...
Expression and Circular Dichroism Studies of the Extracellular Domain of the (1997)
Subunit Of The, Anthony P. West, Pamela J. Bjorkman, Dennis A. Dougherty, Henry A. Lester
this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertise- ment" in accordance with 18 U.S.C. Section 1734 solely to...
Silverman, Scott K., Kofuji, Paulo, Dougherty, Dennis A., Davidson, Norman, Lester, Henry A.
The homozygous weaver mouse displays neuronal degeneration in several brain regions. Previous experiments in heterologous expression systems showed that the G protein-gated inward rectifier K+...
Quick, Michael W., Lester, Henry A., Davidson, Norman, Simon, Melvin I., Aragay, Anna M.
Expression of G protein alpha subunits of the Gq family with various G protein-coupled receptors induces activation of an inositol 1,4,5-trisphosphate (IP3)/Ca2+-mediated Cl- conductance in Xenopus...
Saks, Margaret E., Sampson, Jeffrey R., Nowak, Mark W., Kearney, Patrick C., Du, Fangyong, Abelson, John N., ...
A new tRNA, THG73, has been designed and evaluated as a vehicle for incorporating unnatural amino acids site-specifically into proteins expressed in vivo using the stop codon suppression technique....
In Vivo Incorporation, Margaret E. Saks, Jeffrey R. Sampson, Mark W. Nowak, Patrick C. Kearney, Fangyong Du, ...
this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate...
Xenopus Oocytes, Michael W. Quick, Henry A. Lester, Norman Davidson, Melvin I. Simon, Anna M. Aragay
this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate...
Subunit Stoichiometry of a Heteromultimeric G protein-coupled Inward-rectifier K Channel (1996)
Scott K. Silverman, Henry A. Lester, Dennis A. Dougherty
this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"inaccordance
Ion Binding and Permeation at the GABA Transporter GAT1 (1996)
Sela Mager Nurit, Nurit Kleinberger-doron, Gilmor I. Keshet, Norman Davidson, Baruch I. Kanner, Henry A. Lester
This paper addresses the mechanism of GABA transport by GAT1 (Guastella et al., 1990) and the implications for efficient synaptic transmission. Within a few milliseconds after release, the...
Dascal, Nathan, Doupnik, Craig A., Ivanina, Tatiana, Bausch, Suzanne, Wang, Weizhen, Lin, Catherine, ...
Coexpression in Xenopus oocytes of the inwardly rectifying guanine nucleotide binding (G)-protein-gated K channel GIRK1 with a myristoylated modification of the (putative) cytosolic C-terminal tail...
Kofuji, Paulo, Davidson, Norman, Lester, Henry A.
Guanine nucleotide-binding proteins (G proteins) activate K+ conductances in cardiac atrial cells to slow heart rate and in neurons to decrease excitability. cDNAs encoding three isoforms of a...
Lim, Nancy Fidler, Dascal, Nathan, Labarca, Cesar, Davidson, Norman, Lester, Henry A.
In many tissues, inwardly rectifying K channels are coupled to seven- helix receptors via the Gi/Go family of heterotrimeric G proteins. This activation proceeds at least partially via G beta gamma...
Quick, Michael W., Simon, Melvin I., Davidson, Norman, Lester, Henry A., Aragay, Anna M.
Xenopus oocytes were used to examine the coupling of the serotonin 1c (5HT1c) and thyrotropin-releasing hormone (TRH) receptors to both endogenous and heterologously expressed G protein alpha...
Bradley, Jonathan, Li, Jun, Davidson, Norman, Lester, Henry A., Zinn, Kai
Olfactory receptor neurons respond to odorant stimulation with a rapid increase in intracellular cAMP that opens cyclic nucleotide-gated (cng) cation channels. cng channels in rat olfactory neurons...
Corey, Janis L., Davidson, Norman, Lester, Henry A., Brecha, Nicholas, Quick, Michael W.
We report that activators and inhibitors of protein kinase C (PKC) and protein phosphatases regulate the activity of a cloned rat brain gamma- aminobutyric acid (GABA) transporter (GAT1) expressed in...
Atrial G protein-activated K+ channel: expression cloning and molecular properties (1993)
Dascal, Nathan, Schreibmayer, Wolfgang, Lim, Nancy F., Wang, Weizhen, Chavkin, Charles, DiMagno, Lisa, ...
Activity of several ion channels is controlled by heterotrimeric GTP-binding proteins (G proteins) via a membrane-delimited pathway that does not involve cytoplasmic intermediates. The best studied...
Expression of an atrial G-protein-activated potassium channel in Xenopus oocytes (1993)
Dascal, Nathan, Lim, Nancy F., Schreibmayer, Wolfgang, Wang, Weizhen, Davidson, Norman, Lester, Henry A.
Injection of rat atrial RNA into Xenopus oocytes resulted in the expression of a guanine nucleotide binding (G) protein-activated K+ channel. Current through the channel could be activated by...
Cohen, Bruce N., Labarca, Cesar, Davidson, Norman, Lester, Henry A.
We measured the permeability ratios (PX/PNa) of 3 wild-type, 1 hybrid, 2 subunit-deficient, and 22 mutant nicotinic receptors expressed in Xenopus oocytes for alkali metal and organic cations using...
Cloning, expression, and localization of a rat brain high-affinity glycine transporter (1992)
Guastella, John, Brecha, Nicholas, Weigmann, Christine, Lester, Henry A., Davidson, Norman
A cDNA clone encoding a glycine transporter has been isolated from rat brain by a combined PCR and plaque-hybridization strategy. mRNA synthesized from this clone (designated GLYT1) directs the...
Cohen, Bruce N., Labarca, Cesar, Czyzyk, Linda, Davidson, Norman, Lester, Henry A.
Tris+/Na+ permeability ratios were measured from shifts in the biionic reversal potentials of the macroscopic ACh-induced currents for 3 wild- type (WT), 1 hybrid, 2 subunit-deficient, and 25 mutant...
Strategies for studying permeation at voltage-gated ion channels (1991)
Voltage-dependent ion channels are presently thought to consist of several distinct functional regions: (a) activation gates, (b) inactivation gates, and permeation pathways. This chapter focuses on...
Heterologously expressed serotonin 1A receptors couple to muscarinic K+ channels in heart (1991)
Karschin, Andreas, Ho, Begonia Y., Labarca, Cesar, Elroy-Stein, Orna, Moss, Bernard, Davidson, Norman, ...
In cardiac atrial cells, muscarinic acetylcholine receptors activate a K+ current directly via a guanine nucleotide-binding protein (G protein). Serotonin type 1A receptors may activate a similar...
Both sodium channel II and IIA alpha subunits are expressed in rat brain (1990)
Ahmed, C. M. Lqbal, Auld, Vanessa J., Lester, Henry A., Dunn, Robert, Davidson, Norman
Complementary DNAs encoding four distinct isoforms of the large (α) subunit of the voltage sensitive sodium channel have been isolated from rat brain mRNA (1,2,3). Two of these, II and HA, differ in...
Inactivation of cloned Na channels expressed in Xenopus oocytes (1990)
Krafte, Douglas S., Goldin, Alan L., Auld, Vanessa J., Dunn, Robert J., Davidson, Norman, Lester, Henry A.
This study investigates the inactivation properties of Na channels expressed in Xenopus oocytes from two rat IIA Na channel cDNA clones differing by a single amino acid residue. Although the two...
Rat brain expresses a heterogeneous family of calcium channels (1990)
Snutch, Terry P., Leonard, John P., Gilbert, Mary M., Lester, Henry A., Davidson, Norman
We describe the isolation and characterization of several rat brain cDNAs that are homologous to the 1 subunit of heart and skeletal muscle dihydropyridine-sensitive Ca channels. Northern blot...
Both sodium channel II and IIA alpha subunits are expressed in rat brain (1990)
Ahmed, C.M.Iqbal, Auld, Vanessa J., Lester, Henry A., Dunn, Robert, Davidson, Norman
Functional expression of the yeast alpha-factor receptor in Xenopus oocytes (1989)
Yu, Lei, Blumer, Kendall J., Davidson, Norman, Lester, Henry A., Thorner, Jeremy
The STE2 gene of the yeast Saccharomyces cerevisiae encodes a 431- residue polypeptide that has been shown by chemical cross-linking and genetic studies to be a component of the receptor for the...
Lübbert, Hermann, Hoffman, Beth J., Snutch, Terry P., Van Dyke, Terry, Levine, Arnold J., Hartig, Paul R., ...
We describe a strategy for the cloning of neurotransmitter-receptor and ion-channel cDNAs that is based on electrophysiological assays of mRNA-injected Xenopus oocytes. This procedure circumvents the...
Gurney, Alison M., Tsien, Roger Y., Lester, Henry A.
Although Ca2+ is a well-established intracellular messenger, there are many questions concerning the kinetics and spatial localization of its effects. Such problems may now be approached with the...
Goldin, Alan L., Snutch, Terry P., Lübbert, Hermann, Dowsett, Andrew, Marshall, John, Auld, Vanessa, ...
Several cDNA clones coding for the high molecular weight (alpha) subunit of the voltage-sensitive Na channel have been selected by immunoscreening a rat brain cDNA library constructed in the...
Dascal, Nathan, Lotan, Ilana, Gillo, Boaz, Lester, Henry A., Lass, Yoram
In Xenopus laevis oocytes, adenosine and other purinergic agonists induce a K+-conductance increase that is fully mimicked by intracellular application of cAMP. Acetylcholine suppresses the...
White, Michael M., Mayne, Katharine Mixter, Lester, Henry A., Davidson, Norman
The nicotinic acetylcholine (AcCho) receptor (AcChoR) is a multisubunit protein complex of stoichiometry alpha 2ß gamma delta . The several subunits show homology with each other within a given...
Nargeot, Joel, Nerbonne, Jeanne M., Engels, Joachim, Lester, Henry A.
Voltage-clamped atrial trabeculae from bullfrog hearts were exposed to membrane-permeant photolyzable o-nitrobenzyl esters of cAMP and cGMP. UV flashes produced intracellular concentration jumps of...
Nargeot, Joel, Lester, Henry A., Birdsall, Nigel J. M., Stockton, Jane, Wassermann, Norbert H., Erlanger, Bernard F.
These experiments employ the photoisomerizable compound, 3,3'-bis- [alpha-(trimethylammonium)methyl]azobenzene (Bis-Q), to study the response to muscarinic agents in frog myocardium. In homogenates...
Lester, Henry A., Steer, Michael L., Levitzki, Alexander
In membranes purified from human blood platelets, basal guanosine triphosphate (GTP) hydrolysis is reduced by a factor of approx 6 by exposure to N-ethylmaleimide (10 mM). This decreased background...
Lester, Henry A., Krouse, Mauri E., Nass, Menasche M., Wassermann, Norbert H., Erlanger, Bernard F.
After disulphide bonds are reduced with dithiothreitol, trans-3-(alpha-bromomethyl)-3’-[alpha-(trimethylammonium)methyl]azobenzene (trans-QBr) alkylates a sulfhydryl group on receptors. The...
Lester, Henry A., Krouse, Mauri E., Nass, Menasche M., Wassermann, Norbert H., Erlanger, Bernard F.
After disulphide bonds are reduced with dithiothreitol, trans-3-(alpha-bromomethyl)-3’-[alpha-(trimethylammonium)methyl]azobenzene (trans-QBr) alkylates a sulfhydryl group on receptors. The...
Cholinergic agonists cause an increase in the membrane permeability of Na and K at the innervated face of Electrophorus electroplaques. Therefore, sustained exposure to agonist reduces Na and K...
Cholinergic agonists cause an increase in the membrane permeability of Na and K at the innervated face of Electrophorus electroplaques. Therefore, sustained exposure to agonist reduces Na and K...
Relaxation measurements on the acetylcholine receptor (1975)
Sheridan, Robert E., Lester, Henry A.
In Electrophorus electroplaques, the agonist-induced postsynaptic conductance depends on membrane potential. During steady exposure to agonists, after a voltage step the conductance relaxes on a...
Lester, Henry A., Changeux, Jean-Pierre, Sheridan, Robert E.
When solutions containing agonists are applied to the innervated face of an Electrophorus electroplaque, the membrane's conductance increases. The agonist-induced conductance is increased at more...
Lester, Henry A., Changeux, Jean-Pierre, Sheridan, Robert E.
When solutions containing agonists are applied to the innervated face of an Electrophorus electroplaque, the membrane's conductance increases. The agonist-induced conductance is increased at more...
Ehrengruber, Markus U., Doupnik, Craig A., Xu, Youfeng, Garvey, Justine, Jasek, Mark C., Lester, Henry A., ...
G protein-gated inward rectifier K+ channel subunits 1–4 (GIRK1–4) have been cloned from neuronal and atrial tissue and function as heterotetramers. To examine the inhibition of neuronal...
Zhong, Wenge, Gallivan, Justin P., Zhang, Yinong, Li, Lintong, Lester, Henry A., Dougherty, Dennis A.
The nicotinic acetylcholine receptor is the prototype ligand-gated ion channel. A number of aromatic amino acids have been identified as contributing to the agonist binding site, suggesting that...
RGS proteins reconstitute the rapid gating kinetics of Gβγ-activated inwardly rectifying K+ channels
Doupnik, Craig A., Davidson, Norman, Lester, Henry A., Kofuji, Paulo
G protein-gated inward rectifier K+ (GIRK) channels mediate hyperpolarizing postsynaptic potentials in the nervous system and in the heart during activation of Gα(i/o)-coupled receptors. In neurons...
Site-specific, photochemical proteolysis applied to ion channels in vivo
England, Pamela M., Lester, Henry A., Davidson, Norman, Dougherty, Dennis A.
A method for site-specific, nitrobenzyl-induced photochemical proteolysis of diverse proteins expressed in living cells has been developed based on the chemistry of the unnatural amino acid...
Li, Yong-Xin, Xu, Youfeng, Ju, Donghong, Lester, Henry A., Davidson, Norman, Schuman, Erin M.
We have developed a method to analyze the relative contributions of pre- and postsynaptic actions of a particular gene product in neurons in culture and potentially in slices using...
Labarca, Cesar, Schwarz, Johannes, Deshpande, Purnima, Schwarz, Sigrid, Nowak, Mark W., Fonck, Carlos, ...
Knock-in mice were generated that harbored a leucine-to-serine mutation in the α4 nicotinic receptor near the gate in the channel pore. Mice with intact expression of this hypersensitive receptor...
Yu, Tzu-ping, McKinney, Sheri, Lester, Henry A., Davidson, Norman
cAMP induces a protein-synthesis-dependent late phase of long-term potentiation (LTP) at CA3–CA1 synapses in acute hippocampal slices. Herein we report cAMP-mediated LTP and long-term depression...
Khakh, Baljit S., Smith, W. Bryan, Chiu, Chi-Sung, Ju, Donghong, Davidson, Norman, Lester, Henry A.
ATP-gated P2X2 receptors are widely expressed in neurons, but the cellular effects of receptor activation are unclear. We engineered functional green fluorescent protein (GFP)-tagged P2X2 receptors...
Insights into channel function via channel dysfunction
Leite, John F., Rodrigues-Pinguet, Nivalda, Lester, Henry A.
Leite, John F., Blanton, Michael P., Shahgholi, Mona, Dougherty, Dennis A., Lester, Henry A.
We characterized the differential accessibility of the nicotinic acetylcholine receptor α1 subunit in the open, closed, and desensitized states by using electrophysiology-coordinated photolabeling...
Clayton, Daniel, Shapovalov, George, Maurer, Joshua A., Dougherty, Dennis A., Lester, Henry A., Kochendoerfer, Gerd G.
Total chemical protein synthesis was used to generate multimilligram quantities of the mechanosensitive channel of large conductance from Escherichia coli (Ec-MscL) and Mycobacterium tuberculosis...
Dahan, David S., Dibas, Mohammed I., Petersson, E. James, Auyeung, Vincent C., Chanda, Baron, Bezanilla, Francisco, ...
To study conformational transitions at the muscle nicotinic acetylcholine (ACh) receptor (nAChR), a rhodamine fluorophore was tethered to a Cys side chain introduced at the β19′ position in the M2...
Jankowsky, Joanna L, Slunt, Hilda H, Gonzales, Victoria, Savonenko, Alena V, Wen, Jason C, Jenkins, Nancy A, ...
In a transgenic mouse that overexpressed amyloid beta, turning off production via a tetracycline sensitive switch did not decrease the number of amyloid plaques present
Early fluorescence signals detect transitions at mammalian serotonin transporters.
The mammalian serotonin transporters rSERT or hSERT were expressed in oocytes and labeled with sulforhodamine-MTS. The endogenous Cys-109 residue contributes most of the signal, and the labeled...
Shapovalov, George, Bass, Randal, Rees, Douglas C., Lester, Henry A.
The mechanosensitive channel of large conductance from Mycobacterium tuberculosis (Tb-MscL) was subjected to cysteine-scanning mutagenesis at several residues in the M1 region. The V15C channel...
MALDI-TOF mass spectrometry methods for evaluation of in vitro aminoacyl tRNA production.
Petersson, E James, Shahgholi, Mona, Lester, Henry A, Dougherty, Dennis A
Unnatural amino acid mutagenesis requires the in vitro production of aminoacyl tRNAs. Bacteriophage T4 RNA ligase is used to ligate a-amino-protected dCA amino acids to 74mer tRNA. Previously, there...
In vivo incorporation of multiple unnatural amino acids through nonsense and frameshift suppression
Rodriguez, Erik A., Lester, Henry A., Dougherty, Dennis A.
Site-specific incorporation of unnatural amino acids (UAAs) into proteins is a valuable tool for studying structure–function relationships, incorporating biophysical probes, and elucidating...
Ehrengruber, Markus U., Doupnik, Craig A., Xu, Youfeng, Garvey, Justine, Jasek, Mark C., Lester, Henry A., ...
G protein-gated inward rectifier K+ channel subunits 1–4 (GIRK1–4) have been cloned from neuronal and atrial tissue and function as heterotetramers. To examine the inhibition of neuronal...
Zhong, Wenge, Gallivan, Justin P., Zhang, Yinong, Li, Lintong, Lester, Henry A., Dougherty, Dennis A.
The nicotinic acetylcholine receptor is the prototype ligand-gated ion channel. A number of aromatic amino acids have been identified as contributing to the agonist binding site, suggesting that...
RGS proteins reconstitute the rapid gating kinetics of Gβγ-activated inwardly rectifying K+ channels
Doupnik, Craig A., Davidson, Norman, Lester, Henry A., Kofuji, Paulo
G protein-gated inward rectifier K+ (GIRK) channels mediate hyperpolarizing postsynaptic potentials in the nervous system and in the heart during activation of Gα(i/o)-coupled receptors. In neurons...
Site-specific, photochemical proteolysis applied to ion channels in vivo
England, Pamela M., Lester, Henry A., Davidson, Norman, Dougherty, Dennis A.
A method for site-specific, nitrobenzyl-induced photochemical proteolysis of diverse proteins expressed in living cells has been developed based on the chemistry of the unnatural amino acid...
Li, Yong-Xin, Xu, Youfeng, Ju, Donghong, Lester, Henry A., Davidson, Norman, Schuman, Erin M.
We have developed a method to analyze the relative contributions of pre- and postsynaptic actions of a particular gene product in neurons in culture and potentially in slices using...
Labarca, Cesar, Schwarz, Johannes, Deshpande, Purnima, Schwarz, Sigrid, Nowak, Mark W., Fonck, Carlos, ...
Knock-in mice were generated that harbored a leucine-to-serine mutation in the α4 nicotinic receptor near the gate in the channel pore. Mice with intact expression of this hypersensitive receptor...
Yu, Tzu-ping, McKinney, Sheri, Lester, Henry A., Davidson, Norman
cAMP induces a protein-synthesis-dependent late phase of long-term potentiation (LTP) at CA3–CA1 synapses in acute hippocampal slices. Herein we report cAMP-mediated LTP and long-term depression...
Khakh, Baljit S., Smith, W. Bryan, Chiu, Chi-Sung, Ju, Donghong, Davidson, Norman, Lester, Henry A.
ATP-gated P2X2 receptors are widely expressed in neurons, but the cellular effects of receptor activation are unclear. We engineered functional green fluorescent protein (GFP)-tagged P2X2 receptors...
Insights into channel function via channel dysfunction
Leite, John F., Rodrigues-Pinguet, Nivalda, Lester, Henry A.
Leite, John F., Blanton, Michael P., Shahgholi, Mona, Dougherty, Dennis A., Lester, Henry A.
We characterized the differential accessibility of the nicotinic acetylcholine receptor α1 subunit in the open, closed, and desensitized states by using electrophysiology-coordinated photolabeling...
Clayton, Daniel, Shapovalov, George, Maurer, Joshua A., Dougherty, Dennis A., Lester, Henry A., Kochendoerfer, Gerd G.
Total chemical protein synthesis was used to generate multimilligram quantities of the mechanosensitive channel of large conductance from Escherichia coli (Ec-MscL) and Mycobacterium tuberculosis...
Dahan, David S., Dibas, Mohammed I., Petersson, E. James, Auyeung, Vincent C., Chanda, Baron, Bezanilla, Francisco, ...
To study conformational transitions at the muscle nicotinic acetylcholine (ACh) receptor (nAChR), a rhodamine fluorophore was tethered to a Cys side chain introduced at the β19′ position in the M2...
Jankowsky, Joanna L, Slunt, Hilda H, Gonzales, Victoria, Savonenko, Alena V, Wen, Jason C, Jenkins, Nancy A, ...
In a transgenic mouse that overexpressed amyloid beta, turning off production via a tetracycline sensitive switch did not decrease the number of amyloid plaques present
Early fluorescence signals detect transitions at mammalian serotonin transporters.
The mammalian serotonin transporters rSERT or hSERT were expressed in oocytes and labeled with sulforhodamine-MTS. The endogenous Cys-109 residue contributes most of the signal, and the labeled...
Shapovalov, George, Bass, Randal, Rees, Douglas C., Lester, Henry A.
The mechanosensitive channel of large conductance from Mycobacterium tuberculosis (Tb-MscL) was subjected to cysteine-scanning mutagenesis at several residues in the M1 region. The V15C channel...
MALDI-TOF mass spectrometry methods for evaluation of in vitro aminoacyl tRNA production.
Petersson, E James, Shahgholi, Mona, Lester, Henry A, Dougherty, Dennis A
Unnatural amino acid mutagenesis requires the in vitro production of aminoacyl tRNAs. Bacteriophage T4 RNA ligase is used to ligate a-amino-protected dCA amino acids to 74mer tRNA. Previously, there...
In vivo incorporation of multiple unnatural amino acids through nonsense and frameshift suppression
Rodriguez, Erik A., Lester, Henry A., Dougherty, Dennis A.
Site-specific incorporation of unnatural amino acids (UAAs) into proteins is a valuable tool for studying structure–function relationships, incorporating biophysical probes, and elucidating...
A Cation–π Interaction between Extracellular TEA and an Aromatic Residue in Potassium Channels
Ahern, Christopher A., Eastwood, Amy L., Lester, Henry A., Dougherty, Dennis A., Horn, Richard
Open-channel blockers such as tetraethylammonium (TEA) have a long history as probes of the permeation pathway of ion channels. High affinity blockade by extracellular TEA requires the presence of an...
Gating Transitions in Bacterial Ion Channels Measured at 3 μs Resolution
Shapovalov, George, Lester, Henry A.
Ion channels of high conductance (>200 pS) are widespread among prokaryotes and eukaryotes. Two examples, the Escherichia coli mechanosensitive ion channels Ec-MscS and Ec-MscL, pass currents of...
Rodriguez, Erik A., Lester, Henry A., Dougherty, Dennis A.
The incorporation of unnatural amino acids site-specifically is a valuable technique for structure–function studies, incorporation of biophysical probes, and determining protein–protein...
Rodriguez, Erik A., Lester, Henry A., Dougherty, Dennis A.
The incorporation of unnatural amino acids into proteins is a valuable tool for addition of biophysical probes, bio-orthogonal functionalities, and photoreactive cross-linking agents, although these...
Tong, Yanhe, Brandt, Gabriel S., Li, Ming, Shapovalov, George, Slimko, Eric, Karschin, Andreas, ...
Tyrosine side chains participate in several distinct signaling pathways, including phosphorylation and membrane trafficking. A nonsense suppression procedure was used to incorporate a caged tyrosine...
Li, Ming, Farley, Robert A., Lester, Henry A.
The rat γ-aminobutyric acid transporter GAT1 expressed in Xenopus oocytes was labeled at Cys74, and at one or more other sites, by tetramethylrhodamine-5-maleimide, without significantly altering...
Control of P2X2 Channel Permeability by the Cytosolic Domain
Eickhorst, Angela N., Berson, Amy, Cockayne, Debra, Lester, Henry A., Khakh, Baljit S.
ATP-gated P2X channels are the simplest of the three families of transmitter-gated ion channels. Some P2X channels display a time- and activation-dependent change in permeability as they undergo the...
Five ADNFLE mutations reduce the Ca2+ dependence of the mammalian α4β2 acetylcholine response
Rodrigues-Pinguet, Nivalda, Jia, Li, Li, Maureen, Figl, Antonio, Klaassen, Alwin, Truong, Anthony, ...
Five nicotinic acetylcholine receptor (nAChR) mutations are currently linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). The similarity of their clinical symptoms suggests that a...
Bohland, Jason W., Wu, Caizhi, Barbas, Helen, Bokil, Hemant, Bota, Mihail, Breiter, Hans C., ...
In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is critical, however, for both basic and clinical research into brain function....