Vachon, Eric, Martin, Raiza, Kwok, Vivian, Cherepanov, Vera, Chow, Chung-Wai, Doerschuk, Claire M., ...
Diverse receptors, including Fcgamma receptors and beta(2) integrins (complement receptor-3 [CR3], CD11b/CD18), have been implicated in phagocytosis, but their distinct roles and interactions with...
Signaling to localized degranulation in neutrophils adherent to immune complexes. (2002)
Nauclér, Claes, Grinstein, Sergio, Sundler, Roger, Tapper, Hans
The present study demonstrates that the secretion of azurophilic granules occurring during Fc receptor-mediated attachment and spreading of neutrophils is highly localized to the adhering region of...
Tapper, Hans, Furuya, Wendy, Grinstein, Sergio
The uptake and killing of bacteria by human neutrophils are dependent on the fusion of secretory granules with forming phagosomes. The earliest component of exocytosis was found to precede phagosome...
FcgammaR-Mediated Phagocytosis Stimulates Localized Pinocytosis in Human Neutrophils. (2002)
Botelho, Roberto J, Tapper, Hans, Furuya, Wendy, Mojdami, Donna, Grinstein, Sergio
Abstract not available.
Noninvasive measurement of the pH of the endoplasmic reticulum at rest and during calcium release
Kim, Jae Hong, Johannes, Ludger, Goud, Bruno, Antony, Claude, Lingwood, Clifford A., Daneman, Richard, ...
The pH within individual organelles of the secretory pathway is believed to be an important determinant of their biosynthetic activity. However, little is known about the determinants and regulation...
v-SNARE-dependent secretion is required for phagocytosis
Hackam, David J., Rotstein, Ori D., Sjolin, Carola, Schreiber, Alan D., Trimble, William S., Grinstein, Sergio
Phagosomes are generally believed to form by gradual apposition of the plasma membrane of leukocytes onto the surface of invading microorganisms. The internalization of the encapsulated particle is...
Kiefer, Friedemann, Brumell, John, Al-Alawi, Nadia, Latour, Sylvain, Cheng, Alec, Veillette, André, ...
The cytoplasmic protein tyrosine kinase Syk has two amino-terminal SH2 domains that engage phosphorylated immunoreceptor tyrosine-based activation motifs in the signaling subunits of immunoreceptors....
Functional Expression of Nramp1 In Vitro in the Murine Macrophage Line RAW264.7
Govoni, Gregory, Canonne-Hergaux, François, Pfeifer, Cheryl G., Marcus, Sandra L., Mills, Scott D., Hackam, David J., ...
Mutations at the Nramp1 locus in vivo cause susceptibility to infection by unrelated intracellular microbes. Nramp1 encodes an integral membrane protein abundantly expressed in the...
Contrasting requirements for ubiquitylation during Fc receptor-mediated endocytosis and phagocytosis
Booth, James W., Kim, Moo-Kyung, Jankowski, Andrzej, Schreiber, Alan D., Grinstein, Sergio
Fc receptors on leukocytes mediate internalization of antibody-containing complexes. Soluble immune complexes are taken up by endocytosis, while large antibody-opsonized particles are internalized by...
Modulation of Rab5 and Rab7 Recruitment to Phagosomes by Phosphatidylinositol 3-Kinase
Vieira, Otilia V., Bucci, Cecilia, Harrison, Rene E., Trimble, William S., Lanzetti, Letizia, Gruenberg, Jean, ...
Phagosomal biogenesis is central for microbial killing and antigen presentation by leukocytes. However, the molecular mechanisms governing phagosome maturation are poorly understood. We analyzed the...
Iron chelators modulate the fusogenic properties of Salmonella-containing phagosomes
Jabado, Nada, Cuellar-Mata, Patricia, Grinstein, Sergio, Gros, Philippe
In macrophages, the divalent cations transporter Nramp1 is recruited from the lysosomal compartment to the membrane of phagosomes formed in these cells. Nramp1 mutations cause susceptibility to...
Harrison, Rene E., Bucci, Cecilia, Vieira, Otilia V., Schroer, Trina A., Grinstein, Sergio
Nascent phagosomes must undergo a series of fusion and fission reactions to acquire the microbicidal properties required for the innate immune response. Here we demonstrate that this maturation...
Acquisition of Hrs, an Essential Component of Phagosomal Maturation, Is Impaired by Mycobacteria
Vieira, Otilia V., Harrison, Rene E., Scott, Cameron C., Stenmark, Harald, Alexander, David, Liu, Jun, ...
Pathogenic mycobacteria survive within macrophages by precluding the fusion of phagosomes with late endosomes or lysosomes. Because the molecular determinants of normal phagolysosome formation are...
Salmonella Impairs RILP Recruitment to Rab7 during Maturation of Invasion Vacuoles
Harrison, Rene E., Brumell, John H., Khandani, Arian, Bucci, Cecilia, Scott, Cameron C., Jiang, Xiuju, ...
After invasion of epithelial cells, Salmonella enterica Typhimurium resides within membrane-bound vacuoles where it survives and replicates. Like endocytic vesicles, the Salmonella-containing...
Role of Ubiquitin and Proteasomes in Phagosome Maturation
Lee, Warren L., Kim, Moo-Kyung, Schreiber, Alan D., Grinstein, Sergio
Phagosomes undergo multiple rounds of fusion with compartments of the endocytic pathway during the course of maturation. Despite the insertion of vast amounts of additional membrane, the phagosomal...
Coronin-1 Function Is Required for Phagosome Formation
Yan, Ming, Collins, Richard F., Grinstein, Sergio, Trimble, William S.
Coronin-1 is an actin-associated protein whose function in actin dynamics has remained obscure. All coronin proteins have a variable N-terminal domain, followed by WD repeats and a C-terminal...
Alexander, R. Todd, Furuya, Wendy, Szászi, Katalin, Orlowski, John, Grinstein, Sergio
Proximal tubular reabsorption of filtered sodium by the sodium/hydrogen exchanger isoform 3 (NHE3), located on the apical membrane, is fundamental to the maintenance of systemic volume and pH...
Phagosome maturation: aging gracefully.
Vieira, Otilia V, Botelho, Roberto J, Grinstein, Sergio
Foreign particles and apoptotic bodies are eliminated from the body by phagocytic leucocytes. The initial stage of the elimination process is the internalization of the particles into a plasma...
Martin-Orozco, Natalia, Touret, Nicolas, Zaharik, Michael L., Park, Edwin, Kopelman, Raoul, Miller, Samuel, ...
The objective of these studies was to analyze the role of the ionic environment of phagosomal vacuoles in the control of pathogens by macrophages. Digital imaging and flow cytometry were used to...
Noninvasive measurement of the pH of the endoplasmic reticulum at rest and during calcium release
Kim, Jae Hong, Johannes, Ludger, Goud, Bruno, Antony, Claude, Lingwood, Clifford A., Daneman, Richard, ...
The pH within individual organelles of the secretory pathway is believed to be an important determinant of their biosynthetic activity. However, little is known about the determinants and regulation...
v-SNARE-dependent secretion is required for phagocytosis
Hackam, David J., Rotstein, Ori D., Sjolin, Carola, Schreiber, Alan D., Trimble, William S., Grinstein, Sergio
Phagosomes are generally believed to form by gradual apposition of the plasma membrane of leukocytes onto the surface of invading microorganisms. The internalization of the encapsulated particle is...
Kiefer, Friedemann, Brumell, John, Al-Alawi, Nadia, Latour, Sylvain, Cheng, Alec, Veillette, André, ...
The cytoplasmic protein tyrosine kinase Syk has two amino-terminal SH2 domains that engage phosphorylated immunoreceptor tyrosine-based activation motifs in the signaling subunits of immunoreceptors....
Functional Expression of Nramp1 In Vitro in the Murine Macrophage Line RAW264.7
Govoni, Gregory, Canonne-Hergaux, François, Pfeifer, Cheryl G., Marcus, Sandra L., Mills, Scott D., Hackam, David J., ...
Mutations at the Nramp1 locus in vivo cause susceptibility to infection by unrelated intracellular microbes. Nramp1 encodes an integral membrane protein abundantly expressed in the...
Contrasting requirements for ubiquitylation during Fc receptor-mediated endocytosis and phagocytosis
Booth, James W., Kim, Moo-Kyung, Jankowski, Andrzej, Schreiber, Alan D., Grinstein, Sergio
Fc receptors on leukocytes mediate internalization of antibody-containing complexes. Soluble immune complexes are taken up by endocytosis, while large antibody-opsonized particles are internalized by...
Modulation of Rab5 and Rab7 Recruitment to Phagosomes by Phosphatidylinositol 3-Kinase
Vieira, Otilia V., Bucci, Cecilia, Harrison, Rene E., Trimble, William S., Lanzetti, Letizia, Gruenberg, Jean, ...
Phagosomal biogenesis is central for microbial killing and antigen presentation by leukocytes. However, the molecular mechanisms governing phagosome maturation are poorly understood. We analyzed the...
Iron chelators modulate the fusogenic properties of Salmonella-containing phagosomes
Jabado, Nada, Cuellar-Mata, Patricia, Grinstein, Sergio, Gros, Philippe
In macrophages, the divalent cations transporter Nramp1 is recruited from the lysosomal compartment to the membrane of phagosomes formed in these cells. Nramp1 mutations cause susceptibility to...
Harrison, Rene E., Bucci, Cecilia, Vieira, Otilia V., Schroer, Trina A., Grinstein, Sergio
Nascent phagosomes must undergo a series of fusion and fission reactions to acquire the microbicidal properties required for the innate immune response. Here we demonstrate that this maturation...
Acquisition of Hrs, an Essential Component of Phagosomal Maturation, Is Impaired by Mycobacteria
Vieira, Otilia V., Harrison, Rene E., Scott, Cameron C., Stenmark, Harald, Alexander, David, Liu, Jun, ...
Pathogenic mycobacteria survive within macrophages by precluding the fusion of phagosomes with late endosomes or lysosomes. Because the molecular determinants of normal phagolysosome formation are...
Salmonella Impairs RILP Recruitment to Rab7 during Maturation of Invasion Vacuoles
Harrison, Rene E., Brumell, John H., Khandani, Arian, Bucci, Cecilia, Scott, Cameron C., Jiang, Xiuju, ...
After invasion of epithelial cells, Salmonella enterica Typhimurium resides within membrane-bound vacuoles where it survives and replicates. Like endocytic vesicles, the Salmonella-containing...
Role of Ubiquitin and Proteasomes in Phagosome Maturation
Lee, Warren L., Kim, Moo-Kyung, Schreiber, Alan D., Grinstein, Sergio
Phagosomes undergo multiple rounds of fusion with compartments of the endocytic pathway during the course of maturation. Despite the insertion of vast amounts of additional membrane, the phagosomal...
Coronin-1 Function Is Required for Phagosome Formation
Yan, Ming, Collins, Richard F., Grinstein, Sergio, Trimble, William S.
Coronin-1 is an actin-associated protein whose function in actin dynamics has remained obscure. All coronin proteins have a variable N-terminal domain, followed by WD repeats and a C-terminal...
Alexander, R. Todd, Furuya, Wendy, Szászi, Katalin, Orlowski, John, Grinstein, Sergio
Proximal tubular reabsorption of filtered sodium by the sodium/hydrogen exchanger isoform 3 (NHE3), located on the apical membrane, is fundamental to the maintenance of systemic volume and pH...
Phagosome maturation: aging gracefully.
Vieira, Otilia V, Botelho, Roberto J, Grinstein, Sergio
Foreign particles and apoptotic bodies are eliminated from the body by phagocytic leucocytes. The initial stage of the elimination process is the internalization of the particles into a plasma...
Martin-Orozco, Natalia, Touret, Nicolas, Zaharik, Michael L., Park, Edwin, Kopelman, Raoul, Miller, Samuel, ...
The objective of these studies was to analyze the role of the ionic environment of phagosomal vacuoles in the control of pathogens by macrophages. Digital imaging and flow cytometry were used to...
Quantitative Analysis of Membrane Remodeling at the Phagocytic Cup
Lee, Warren L., Mason, David, Schreiber, Alan D., Grinstein, Sergio
Nascent phagosomes, which are derived from the plasma membrane, acquire microbicidal properties through multiple fusion and fission events collectively known as maturation. Here we show that...
Steinberg, Benjamin E., Touret, Nicolas, Vargas-Caballero, Mariana, Grinstein, Sergio
Phagosomes employ lytic enzymes, cationic peptides, and reactive oxygen intermediates to eliminate invading microorganisms. The effectiveness of these microbicidal mechanisms is potentiated by the...
Smith, Adam C., Heo, Won Do, Braun, Virginie, Jiang, Xiuju, Macrae, Chloe, Casanova, James E., ...
Members of the Rab guanosine triphosphatase (GTPase) family are key regulators of membrane traffic. Here we examined the association of 48 Rabs with model phagosomes containing a non-invasive mutant...
Corbett-Nelson, Elaine F., Mason, David, Marshall, John G., Collette, Yves, Grinstein, Sergio
Phospholipids play a critical role in the recruitment and activation of several adaptors and effectors during phagocytosis. Changes in lipid metabolism during phagocytosis are restricted to the...
LAMP proteins are required for fusion of lysosomes with phagosomes
Huynh, Kassidy K, Eskelinen, Eeva-Liisa, Scott, Cameron C, Malevanets, Anatoly, Saftig, Paul, Grinstein, Sergio
Lysosome-associated membrane proteins 1 and 2 (LAMP-1 and LAMP-2) are delivered to phagosomes during the maturation process. We used cells from LAMP-deficient mice to analyze the role of these...
Golgi-bound Rab34 Is a Novel Member of the Secretory Pathway
Goldenberg, Neil M., Grinstein, Sergio, Silverman, Mel
Golgi-localized Rab34 has been implicated in repositioning lysosomes and activation of macropinocytosis. Using HeLa cells, we undertook a detailed investigation of Rab34 involvement in intracellular...
Suh, Chang-Il, Stull, Natalie D., Li, Xing Jun, Tian, Wei, Price, Marianne O., Grinstein, Sergio, ...
Superoxide produced by the phagocyte reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is essential for host defense. Enzyme activation requires translocation of p67phox, p47phox,...
Mason, David, Mallo, Gustavo V., Terebiznik, Mauricio R., Payrastre, Bernard, Finlay, B. Brett, Brumell, John H., ...
Elucidation of the role of PtdIns(4,5)P2 in epithelial function has been hampered by the inability to selectively manipulate the cellular content of this phosphoinositide. Here we report that SigD, a...
Phosphatidylinositol-4,5-bisphosphate hydrolysis directs actin remodeling during phagocytosis
Scott, Cameron C., Dobson, Wendy, Botelho, Roberto J., Coady-Osberg, Natasha, Chavrier, Philippe, Knecht, David A., ...
The Rho GTPases play a critical role in initiating actin polymerization during phagocytosis. In contrast, the factors directing the disassembly of F-actin required for fission of the phagocytic...
Inhibition and Redistribution of NHE3, the Apical Na+/H+ Exchanger, by Clostridium difficile Toxin B
Hayashi, Hisayoshi, Szászi, Katalin, Coady-Osberg, Natasha, Furuya, Wendy, Bretscher, Anthony P., Orlowski, John, ...
NHE3, the apical isoform of the Na+/H+ exchanger, is central to the absorption of salt and water across the intestinal epithelium. We report that treatment of epithelial cells with toxin B of...
Gruenheid, Samantha, Canonne-Hergaux, François, Gauthier, Susan, Hackam, David J., Grinstein, Sergio, Gros, Philippe
The natural resistance associated macrophage protein (Nramp) gene family is composed of two members in mammals, Nramp1 and Nramp2. Nramp1 is expressed primarily in macrophages and mutations at this...
Jabado, Nada, Jankowski, Andrzej, Dougaparsad, Samuel, Picard, Virginie, Grinstein, Sergio, Gros, Philippe
Mutations at the natural resistance–associated macrophage protein 1 (Nramp1) locus cause susceptibility to infection with antigenically unrelated intracellular pathogens. Nramp1 codes for an...
Zhang, Jinyi, Shehabeldin, Amro, Butler, Jeffrey, Somani, Ally-Khan, McGavin, Mary, ...
The Wiskott-Aldrich syndrome protein (WASp) has been implicated in modulation of lymphocyte activation and cytoskeletal reorganization. To address the mechanisms whereby WASp subserves such...
Hackam, David J., Rotstein, Ori D., Schreiber, Alan, Zhang, Wei-jian, Grinstein, Sergio
Phagocytosis of bacteria by macrophages and neutrophils is an essential component of host defense against infection. The mechanism whereby the interaction of opsonized particles with Fcγ receptors...
Hackam, David J., Rotstein, Ori D., Zhang, Wei-jian, Gruenheid, Samantha, Gros, Philippe, Grinstein, Sergio
The mechanisms underlying the survival of intracellular parasites such as mycobacteria in host macrophages remain poorly understood. In mice, mutations at the Nramp1 gene (for natural...
Demaurex, Nicolas, Romanek, Robert R., Orlowski, John, Grinstein, Sergio
We studied the ATP dependence of NHE-1, the ubiquitous isoform of the Na+/H+ antiporter, using the whole-cell configuration of the patch-clamp technique to apply nucleotides intracellularly while...
NO3−-induced pH Changes in Mammalian Cells : Evidence for an NO3−-H+ Cotransporter
Chow, Chung-Wai, Kapus, Andras, Romanek, Robert, Grinstein, Sergio
The effect of NO3− on intracellular pH (pHi) was assessed microfluorimetrically in mammalian cells in culture. In cells of human, hamster, and murine origin addition of extracellular NO3− induced...
Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis
Botelho, Roberto J., Teruel, Mary, Dierckman, Renee, Anderson, Richard, Wells, Alan, York, John D., ...
Phagocytosis requires localized and transient remodeling of actin filaments. Phosphoinositide signaling is believed to play an important role in cytoskeletal organization, but it is unclear whether...
Marshall, John G., Booth, James W., Stambolic, Vuk, Mak, Tak, Balla, Tamas, Schreiber, Alan D., ...
Phagocytosis is a highly localized and rapid event, requiring the generation of spatially and temporally restricted signals. Because phosphatidylinositol 3-kinase (PI3K) plays an important role in...
Vieira, Otilia V., Botelho, Roberto J., Rameh, Lucia, Brachmann, Saskia M., Matsuo, Tsuyoshi, Davidson, Howard W., ...
Phagosomes acquire their microbicidal properties by fusion with lysosomes. Products of phosphatidylinositol 3-kinase (PI 3-kinase) are required for phagosome formation, but their role in maturation...
Critical role for scaffolding adapter Gab2 in FcγR-mediated phagocytosis
Gu, Haihua, Botelho, Roberto J., Yu, Min, Grinstein, Sergio, Neel, Benjamin G.
Grb2-associated binder 2 (Gab2), a member of the Dos/Gab subfamily scaffolding molecules, plays important roles in regulating the growth, differentiation, and function of many hematopoietic cell...
Golgi Alkalinization by the Papillomavirus E5 Oncoprotein
Schapiro, Florencia, Sparkowski, Jason, Adduci, Alex, Suprynowicz, Frank, Schlegel, Richard, Grinstein, Sergio
The E5 oncoprotein of bovine papillomavirus type I is a small, hydrophobic polypeptide localized predominantly in the Golgi complex. E5-mediated transformation is often associated with activation of...
Focal Exocytosis of Vamp3-Containing Vesicles at Sites of Phagosome Formation
Bajno, Lydia, Peng, Xiao-Rong, Schreiber, Alan D., Moore, Hsiao-Ping, Trimble, William S., Grinstein, Sergio
Phagocytosis involves the receptor-mediated extension of plasmalemmal protrusions, called pseudopods, which fuse at their tip to engulf a particle. Actin polymerizes under the nascent phagosome and...
Intracellular Ph Regulation by Na+/H+ Exchange Requires Phosphatidylinositol 4,5-Bisphosphate
Aharonovitz, Orit, Zaun, Hans C., Balla, Tamas, York, John D., Orlowski, John, Grinstein, Sergio
The carrier-mediated, electroneutral exchange of Na+ for H+ across the plasma membrane does not directly consume metabolic energy. Nevertheless, acute depletion of cellular ATP markedly decreases...
Mammalian Septins Are Required for Phagosome Formation
Huang, Yi-Wei, Yan, Ming, Collins, Richard F., DiCiccio, Jessica E., Grinstein, Sergio, Trimble, William S.
Septins are members of a highly conserved family of filamentous proteins that are required in many organisms for the completion of cytokinesis. In addition, septins have been implicated in a number...
Steinberg, Benjamin E., Grinstein, Sergio
Phagocytosis is a key component of the innate immune response and of the clearance of apoptotic bodies. Phagosome formation and subsequent maturation require extensive cytoskeletal rearrangement and...
Regulation of Vacuolar pH and Its Modulation by Some Microbial Species
Huynh, Kassidy K., Grinstein, Sergio
Summary: To survive within the host, pathogens such as Mycobacterium tuberculosis and Helicobacter pylori need to evade the immune response and find a protected niche where they are not exposed to...
Vachon, Eric, Martin, Raiza, Kwok, Vivian, Cherepanov, Vera, Chow, Chung-Wai, Doerschuk, Claire M., ...
Diverse receptors, including Fcγ receptors and β2 integrins (complement receptor-3 [CR3], CD11b/CD18), have been implicated in phagocytosis, but their distinct roles and interactions with other...
Mallo, Gustavo V., Espina, Marianela, Smith, Adam C., Terebiznik, Mauricio R., Alemán, Ainel, Finlay, B. Brett, ...
Salmonella colonizes a vacuolar niche in host cells during infection. Maturation of the Salmonella-containing vacuole (SCV) involves the formation of phosphatidylinositol 3-phosphate (PI(3)P) on its...
Abnormalities in the Pulmonary Innate Immune System in Cystic Fibrosis
Moraes, Theo J., Plumb, Jonathan, Martin, Raiza, Vachon, Eric, Cherepanov, Vera, Koh, Adeline, ...
Pulmonary infection is the dominant clinical feature of cystic fibrosis (CF), but the basis for this susceptibility remains incompletely understood. One hypothesis is that CF airway surface liquid...
Sason, Hagit, Milgrom, Michal, Weiss, Aryeh M., Melamed-Book, Naomi, Balla, Tamas, Grinstein, Sergio, ...
Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] are phosphoinositides (PIs) present in small amounts in the inner leaflet of the plasma...
Li, Xing Jun, Tian, Wei, Stull, Natalie D., Grinstein, Sergio, Atkinson, Simon, Dinauer, Mary C.
The assembly of cytosolic p47phox and p67phox with flavocytochrome b558 at the membrane is crucial for activating the leukocyte NADPH oxidase that generates superoxide for microbial killing. p47phox...
Activation of antibacterial autophagy by NADPH oxidases
Huang, Ju, Canadien, Veronica, Lam, Grace Y., Steinberg, Benjamin E., Dinauer, Mary C., Magalhaes, Marco A. O., ...
Autophagy plays an important role in immunity to microbial pathogens. The autophagy system can target bacteria in phagosomes, promoting phagosome maturation and preventing pathogen escape into the...
Tian, Wei, Li, Xing Jun, Stull, Natalie D., Ming, Wenyu, Suh, Chang-Il, Bissonnette, Sarah A., ...
The phagocyte NADPH oxidase generates superoxide for microbial killing, and includes a membrane-bound flavocytochrome b558 and cytosolic p67phox, p47phox, and p40phox subunits that undergo membrane...