Sergio Grinstein
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View article: Lipid scrambling via TMEM16F mediates the formation and release of apoptotic vesicles
Lipid scrambling via TMEM16F mediates the formation and release of apoptotic vesicles Open
The ubiquitous and highly conserved programmed cell death pathways that are essential for tissue development and homeostasis are accompanied by distinct morphological alterations. Apoptotic cells undergo fragmentation that is concomitant w…
View article: Reactive oxygen species suppress phagocyte surveillance by oxidizing cytoskeletal regulators
Reactive oxygen species suppress phagocyte surveillance by oxidizing cytoskeletal regulators Open
Despite their superficial similarities, the phagocytosis of pathogens differs from that of apoptotic cells in their recognition mechanisms and downstream signaling pathways. While the initial stages of these processes have been studied, th…
View article: Reactive oxygen species suppress phagocyte surveillance by oxidizing cytoskeletal regulators
Reactive oxygen species suppress phagocyte surveillance by oxidizing cytoskeletal regulators Open
Despite their superficial similarities, the phagocytosis of pathogens differs from that of apoptotic cells in their recognition mechanisms and downstream signaling pathways. While the initial stages of these processes have been studied, th…
View article: Salmonella exploits membrane reservoirs for invasion of host cells
Salmonella exploits membrane reservoirs for invasion of host cells Open
Salmonella utilizes a type 3 secretion system to translocate virulence proteins (effectors) into host cells during infection 1 . The effectors modulate host cell machinery to drive uptake of the bacteria into vacuoles, where they can estab…
View article: Reactive oxygen species suppress phagocyte surveillance by oxidizing cytoskeletal regulators
Reactive oxygen species suppress phagocyte surveillance by oxidizing cytoskeletal regulators Open
Despite their superficial similarities, the phagocytosis of pathogens differs from that of apoptotic cells in their recognition mechanisms and downstream signaling pathways. While the initial stages of these processes have been studied, th…
View article: Reactive oxygen species suppress phagocyte surveillance by oxidizing cytoskeletal regulators
Reactive oxygen species suppress phagocyte surveillance by oxidizing cytoskeletal regulators Open
Despite their superficial similarities, the phagocytosis of pathogens differs from that of apoptotic cells in their recognition mechanisms and downstream signaling pathways. While the initial stages of these processes have been studied, th…
View article: Adenomatous polyposis coli (APC) regulates internalization and signaling of the chemorepellent receptor, Roundabout (ROBO) 1
Adenomatous polyposis coli (APC) regulates internalization and signaling of the chemorepellent receptor, Roundabout (ROBO) 1 Open
The SLIT-ROBO signaling pathway regulates axon guidance and cell migration, and ROBO1 is a receptor for SLIT ligands. ROBO1 undergoes constitutive endocytosis which is enhanced upon SLIT2 binding, but the molecular mechanisms and functiona…
View article: Target lysis by cholesterol extraction is a rate limiting step in the resolution of phagolysosomes
Target lysis by cholesterol extraction is a rate limiting step in the resolution of phagolysosomes Open
The ongoing phagocytic activity of macrophages necessitates an extraordinary capacity to digest and resolve incoming material. While the initial steps leading to the formation of a terminal phagolysosome are well studied, much less is know…
View article: Respiration supports intraphagosomal filamentation and escape of <i>Candida albicans</i> from macrophages
Respiration supports intraphagosomal filamentation and escape of <i>Candida albicans</i> from macrophages Open
For the human fungal pathogen Candida albicans , metabolic flexibility and the ability to transition between yeast and filamentous growth states are key virulence traits that enable disease in the host. These traits are particularly import…
View article: PB0376 Vacuolar-Type ATPase Dependent Acidification of Megakaryocyte and Platelet α-Granules Maintains Packaging of VWF
PB0376 Vacuolar-Type ATPase Dependent Acidification of Megakaryocyte and Platelet α-Granules Maintains Packaging of VWF Open
Background: Hydroxyurea (HU), α-Interferon (αIFN), anagrelide (ANA) and ruxolitinib (Ruxo) are used in Myeloproliferative Neoplasms (MPN) treatment, conditions associated to thrombosis.Aims: Considering that large platelets could be relate…
View article: The chemorepellent, SLIT2, bolsters innate immunity against Staphylococcus aureus
The chemorepellent, SLIT2, bolsters innate immunity against Staphylococcus aureus Open
Neutrophils are essential for host defense against Staphylococcus aureus ( S. aureus ). The neuro-repellent, SLIT2, potently inhibits neutrophil chemotaxis, and might, therefore, be expected to impair antibacterial responses. We report her…
View article: Author response: The chemorepellent, SLIT2, bolsters innate immunity against Staphylococcus aureus
Author response: The chemorepellent, SLIT2, bolsters innate immunity against Staphylococcus aureus Open
Full text Figures and data Side by side Abstract Editor's evaluation Introduction Results Discussion Materials and methods Appendix 1 Data availability References Decision letter Author response Article and author information Abstract Neut…
View article: Lysosomal swelling and lysis mediate delivery of C3 toxins to their cytoplasmic targets
Lysosomal swelling and lysis mediate delivery of C3 toxins to their cytoplasmic targets Open
Unlike other cholera‐like toxins that contain separate binding/translocation and catalytic subunits, C3‐like mono‐ADP‐ribosyltransferases consist of a single subunit that serves both functions. The manner whereby C3 toxins reach the host c…
View article: ClC-7 drives intraphagosomal chloride accumulation to support hydrolase activity and phagosome resolution
ClC-7 drives intraphagosomal chloride accumulation to support hydrolase activity and phagosome resolution Open
Degradative organelles contain enzymes that function optimally at the acidic pH generated by the V-ATPase. The resulting transmembrane H+ gradient also energizes the secondary transport of several solutes, including Cl−. We report that Cl−…
View article: Endocytosis is regulated through the pH-dependent phosphorylation of Rab GTPases by Parkinson’s kinase LRRK2
Endocytosis is regulated through the pH-dependent phosphorylation of Rab GTPases by Parkinson’s kinase LRRK2 Open
While it has been known for decades that luminal acidification is required for normal traffic along the endocytic pathway, the precise underlying mechanism(s) remain unknown. We found that dissipation of the endomembrane pH gradient result…
View article: Endocytosis is regulated through the pH-dependent phosphorylation of Rab GTPases by Parkinson’s kinase LRRK2
Endocytosis is regulated through the pH-dependent phosphorylation of Rab GTPases by Parkinson’s kinase LRRK2 Open
While it has been known for decades that luminal acidification is required for normal traffic along the endocytic pathway, the precise underlying mechanism(s) remain unknown. We found that dissipation of the endomembrane pH gradient result…
View article: Novel immunodeficiency caused by homozygous mutation in <i>SLC19A1</i> encoding the reduced folate carrier
Novel immunodeficiency caused by homozygous mutation in <i>SLC19A1</i> encoding the reduced folate carrier Open
Letter to Blood| June 29, 2023 Novel immunodeficiency caused by homozygous mutation in solute carrier family 19 member 1, which encodes the reduced folate carrier Akira Shiraishi, Akira Shiraishi 1Division of Immunology and Allergy, Depart…
View article: Localized diacylglycerol-dependent stimulation of Ras and Rap1 during phagocytosis
Localized diacylglycerol-dependent stimulation of Ras and Rap1 during phagocytosis Open
We describe a role for diacylglycerol in the activation of Ras and Rap1 at the phagosomal membrane. During phagocytosis, Ras density was similar on the surface and invaginating areas of the membrane, but activation was detectable only in t…
View article: An electrostatic switch displaces phosphatidylinositol phosphate kinases from the membrane during phagocytosis
An electrostatic switch displaces phosphatidylinositol phosphate kinases from the membrane during phagocytosis Open
Plasmalemmal phosphatidylinositol (PI) 4,5-bisphosphate (PI4,5P(2)) synthesized by PI 4-phosphate (PI4P) 5-kinase (PIP5K) is key to the polymerization of actin that drives chemotaxis and phagocytosis. We investigated the means whereby PIP5…
View article: An electrostatic switch displaces phosphatidylinositol phosphate kinases from the membrane during phagocytosis
An electrostatic switch displaces phosphatidylinositol phosphate kinases from the membrane during phagocytosis Open
Plasmalemmal phosphatidylinositol (PI) 4,5-bisphosphate (PI4,5P(2)) synthesized by PI 4-phosphate (PI4P) 5-kinase (PIP5K) is key to the polymerization of actin that drives chemotaxis and phagocytosis. We investigated the means whereby PIP5…
View article: Localized diacylglycerol-dependent stimulation of Ras and Rap1 during phagocytosis
Localized diacylglycerol-dependent stimulation of Ras and Rap1 during phagocytosis Open
We describe a role for diacylglycerol in the activation of Ras and Rap1 at the phagosomal membrane. During phagocytosis, Ras density was similar on the surface and invaginating areas of the membrane, but activation was detectable only in t…
View article: The chemorepellent, SLIT2, bolsters innate immunity against <i>Staphylococcus aureus</i>
The chemorepellent, SLIT2, bolsters innate immunity against <i>Staphylococcus aureus</i> Open
Neutrophils are essential for host defense against Staphylococcus aureus ( S. aureus ). The neuro-repellent, SLIT2, potently inhibits neutrophil chemotaxis, and might therefore be expected to impair antibacterial responses. We report here …
View article: Lipid peroxidation increases membrane tension, Piezo1 gating and cation permeability to execute ferroptosis
Lipid peroxidation increases membrane tension, Piezo1 gating and cation permeability to execute ferroptosis Open
The ongoing metabolic and microbicidal pathways that support and protect cellular life generate potentially damaging reactive oxygen species (ROS). To counteract damage, cells express peroxidases, antioxidant enzymes that catalyze the redu…
View article: Lysosomal swelling and lysis mediate delivery of C3 toxins to their cytoplasmic targets
Lysosomal swelling and lysis mediate delivery of C3 toxins to their cytoplasmic targets Open
Unlike other cholera-like toxins that contain separate binding/translocation and catalytic subunits, C3-like mono-ADP-ribosyltransferases consist of a single subunit that serves both functions. The manner whereby C3 toxins reach the host c…
View article: PtdIns(3,4)P2, Lamellipodin, and VASP coordinate actin dynamics during phagocytosis in macrophages
PtdIns(3,4)P2, Lamellipodin, and VASP coordinate actin dynamics during phagocytosis in macrophages Open
Phosphoinositides are pivotal regulators of vesicular traffic and signaling during phagocytosis. Phagosome formation, the initial step of the process, is characterized by local membrane remodeling and reorganization of the actin cytoskelet…
View article: CryoEM of endogenous mammalian V-ATPase interacting with the TLDc protein mEAK-7
CryoEM of endogenous mammalian V-ATPase interacting with the TLDc protein mEAK-7 Open
V-ATPases are rotary proton pumps that serve as signaling hubs with numerous protein binding partners. CryoEM with exhaustive focused classification allowed detection of endogenous proteins associated with porcine kidney V-ATPase. An extra…