Sergio Grinstein
University of Toronto
H-index: 143
North America-Canada
Description
Sergio Grinstein, With an exceptional h-index of 143 and a recent h-index of 63 (since 2020), a distinguished researcher at University of Toronto, specializes in the field of cell biology, membranes.
His recent articles reflect a diverse array of research interests and contributions to the field:
Reactive oxygen species suppress phagocyte surveillance by oxidizing cytoskeletal regulators
Redistribution of the glycocalyx exposes phagocytic determinants on apoptotic cells
Adenomatous polyposis coli (APC) regulates internalization and signaling of the chemorepellent receptor, Roundabout (ROBO) 1
Salmonella exploits membrane reservoirs for invasion of host cells
Target lysis by cholesterol extraction is a rate limiting step in the resolution of phagolysosomes
Destructive breakdown studies of irradiated LGADs at beam tests for the ATLAS HGTD
Lipid peroxidation increases membrane tension, Piezo1 gating, and cation permeability to execute ferroptosis
ClC-7 drives intraphagosomal chloride accumulation to support hydrolase activity and phagosome resolution
Professor Information
University | University of Toronto |
---|---|
Position | Senior Scientist, Hospital for Sick Children |
Citations(all) | 76026 |
Citations(since 2020) | 18485 |
Cited By | 65606 |
hIndex(all) | 143 |
hIndex(since 2020) | 63 |
i10Index(all) | 568 |
i10Index(since 2020) | 283 |
University Profile Page | University of Toronto |
Research & Interests List
cell biology
membranes
Top articles of Sergio Grinstein
Reactive oxygen species suppress phagocyte surveillance by oxidizing cytoskeletal regulators
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, the cytoskeletal reorganization that follows particle uptake is not well understood. By comparing the uptake of phosphatidylserine (PS)-coated targets versus IgG-opsonized targets of identical size, shape, and rigidity, we noted remarkable differences in the accompanying changes in cell morphology, adhesion and migration that persisted long after phagocytosis. While myeloid cells continued to survey their microenvironment after engulfing PS-coated targets, the uptake of IgG-opsonized targets caused phagocytes to round up, decreased their membrane ruffling, and led to the complete disassembly of podosomes. These changes were associated with increased activation of Rho and a concomitant decrease of Rac activity that collectively resulted in the thickening and compaction of the cortical F-actin cytoskeleton. Rho/formin-induced actin polymers were fastened to the membrane by their preferential interaction with Ezrin-Radixin-Moesin (ERM) proteins, which were necessary for cell compaction and podosome disassembly following ingestion of IgG-coated particles. The source of the distinct responses to PS-versus IgG-targets was the differential activation of the respiratory burst mediated by the NADPH oxidase: reactive oxygen species (ROS), emanating from phagosomes containing IgG-opsonized targets–but not those containing PS-coated ones–directly led to the activation of Rho. Similar findings were made …
Authors
Sergio Grinstein,Iuliia Ferling,Steffen Pfalzgraf,Lea Moutounet,Lanhui Qiu,Iris Li,Yuhuan Zhou,Spencer Freeman
Published Date
2024/2/22
Redistribution of the glycocalyx exposes phagocytic determinants on apoptotic cells
Phagocytes remove dead and dying cells by engaging "eat-me" ligands such as phosphatidylserine (PtdSer) on the surface of apoptotic targets. However, PtdSer is obscured by the bulky exofacial glycocalyx, which also exposes ligands that activate "don't-eat-me" receptors such as Siglecs. Clearly, unshielding the juxtamembrane "eat-me" ligands is required for the successful engulfment of apoptotic cells, but the mechanisms underlying this process have not been described. Using human and murine cells, we find that apoptosis-induced retraction and weakening of the cytoskeleton that anchors transmembrane proteins cause an inhomogeneous redistribution of the glycocalyx: actin-depleted blebs emerge, lacking the glycocalyx, while the rest of the apoptotic cell body retains sufficient actin to tether the glycocalyx in place. Thus, apoptotic blebs can be engaged by phagocytes and are targeted for engulfment …
Authors
Trieu Le,Iuliia Ferling,Lanhui Qiu,Clement Nabaile,Leonardo Assunção,Calvin D Roskelley,Sergio Grinstein,Spencer A Freeman
Journal
Developmental Cell
Published Date
2024/2/14
Adenomatous polyposis coli (APC) regulates internalization and signaling of the chemorepellent receptor, Roundabout (ROBO) 1
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 functional consequences of this process are not well understood. Using pharmacologic inhibitors and molecular techniques, we found that clathrin-mediated endocytosis is necessary for SLIT2-induced inhibition of cell spreading. To explore the underlying mechanisms, we performed BioID to identify ROBO1-interacting proteins whose association with the cytoplasmic domain of ROBO1 is differentially regulated by SLIT2. We discovered that adenomatous polyposis coli (APC), a multifunctional tumor suppressor, constitutively interacts with ROBO1 but dissociates upon binding of SLIT2 and that this dissociation is necessary for clathrin-mediated endocytosis of ROBO1 and subsequent effects on cell morphology. These findings provide new insights into the functional mechanisms by which SLIT2 binding to ROBO1 effects changes in actin cytoskeletal architecture.
Authors
Yi-Wei Huang,Jonathan St-Germain,Bo Wen Pang,Richard F Collins,Etienne Coyaud,Wenjuan Li,Amir Mohamed,Brian Raught,Sergio Grinstein,Lisa A Robinson
Journal
bioRxiv
Published Date
2024/1/13
Salmonella exploits membrane reservoirs for invasion of host cells
Salmonella utilizes a type 3 secretion system to translocate virulence proteins (effectors) into host cells during infection. The effectors modulate host cell machinery to drive uptake of the bacteria into vacuoles, where they can establish an intracellular replicative niche. A remarkable feature of Salmonella invasion is the formation of actin-rich protuberances (ruffles) on the host cell surface that contribute to bacterial uptake. However, the membrane source for ruffle formation and how these bacteria regulate membrane mobilization within host cells remains unclear. Here, we show that Salmonella exploits membrane reservoirs for the generation of invasion ruffles. The reservoirs are pre-existing tubular compartments associated with the plasma membrane (PM) and are formed through the activity of RAB10 GTPase. Under normal growth conditions, membrane reservoirs contribute to PM homeostasis and are preloaded …
Authors
Hongxian Zhu,Andrew M Sydor,Kirsten C Boddy,Etienne Coyaud,Estelle MN Laurent,Aaron Au,Joel MJ Tan,Bing-Ru Yan,Jason Moffat,Aleixo M Muise,Christopher M Yip,Sergio Grinstein,Brian Raught,John H Brumell
Journal
Nature Communications
Published Date
2024/4/10
Target lysis by cholesterol extraction is a rate limiting step in the resolution of phagolysosomes
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 known about the later stages of this process, namely the degradation and resolution of the phagolysosomal contents. We report that the degradation of targets such as splenocytes and erythrocytes by phagolysosomes occurs in a stepwise fashion, requiring lysis of their plasmalemmal bilayer as an essential initial step. This is achieved by the direct extraction of cholesterol facilitated by Niemann-Pick protein type C2 (NPC2), which in turn hands off cholesterol to NPC1 for export from the phagolysosome. The removal of cholesterol ulimately destabilizes and permeabilizes the membrane of the phagocytic target, allowing access of hydrolases to its internal compartments. In contrast, we …
Authors
Dante Barreda,Sergio Grinstein,Spencer A Freeman
Journal
European Journal of Cell Biology
Published Date
2024/3/1
Destructive breakdown studies of irradiated LGADs at beam tests for the ATLAS HGTD
In the past years, it has been observed at several beam test campaigns that irradiated LGAD sensors break with a typical star shaped burn mark when operated at voltages much lower than those at which they were safely operated during laboratory tests. The study presented in this paper was designed to determine the safe operating voltage that these sensors can withstand. Many irradiated sensors from various producers were tested in two test beam facilities, DESY (Hamburg) and CERN-SPS (Geneva), as part of ATLAS High Granularity Timing Detector (HGTD) beam tests. The samples were placed in the beam and kept under bias over a long period of time in order to reach a high number of particles crossing each sensor. Both beam tests lead to a similar conclusion, that these destructive events begin to occur when the average electric field in the sensor becomes larger than 12 V/μm.
Authors
LA Beresford,DE Boumediene,L Castillo García,LD Corpe,MJ Da Cunha Sargedas de Sousa,H El Jarrari,A Eshkevarvakili,C Grieco,S Grinstein,S Guindon,A Howard,G Kramberger,O Kurdysh,R Mazini,M Missio,M Morenas,O Perrin,V Raskina,G Saito,S Trincaz-Duvoid
Journal
Journal of Instrumentation
Published Date
2023/7/14
Lipid peroxidation increases membrane tension, Piezo1 gating, and cation permeability to execute ferroptosis
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, which are antioxidant enzymes that catalyze the reduction of oxidized biomolecules. Glutathione peroxidase 4 (GPX4) is the major hydroperoxidase specifically responsible for reducing lipid peroxides; this homeostatic mechanism is essential, and its inhibition causes a unique type of lytic cell death, ferroptosis. The mechanism(s) that lead to cell lysis in ferroptosis, however, are unclear. We report that the lipid peroxides formed during ferroptosis accumulate preferentially at the plasma membrane. Oxidation of surface membrane lipids increased tension on the plasma membrane and led to the activation of Piezo1 and TRP channels. Oxidized membranes thus became permeable to cations, ultimately leading to the …
Authors
Yusuke Hirata,Ruiqi Cai,Allen Volchuk,Benjamin E Steinberg,Yoshiro Saito,Atsushi Matsuzawa,Sergio Grinstein,Spencer A Freeman
Journal
Current Biology
Published Date
2023/4/10
ClC-7 drives intraphagosomal chloride accumulation to support hydrolase activity and phagosome resolution
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− influx, driven by the 2Cl−/H+ exchanger ClC-7, is necessary for the resolution of phagolysosomes formed by macrophages. Cl− transported via ClC-7 had been proposed to provide the counterions required for electrogenic H+ pumping. However, we found that deletion of ClC-7 had a negligible effect on phagosomal acidification. Instead, luminal Cl− was found to be required for activation of a wide range of phagosomal hydrolases including proteases, nucleases, and glycosidases. These findings argue that the primary role of ClC-7 is the accumulation of (phago)lysosomal Cl− and that the V-ATPases not only optimize the activity of degradative hydrolases by lowering the pH …
Authors
Jing Ze Wu,Mariia Zeziulia,Whijin Kwon,Thomas J Jentsch,Sergio Grinstein,Spencer A Freeman
Journal
Journal of Cell Biology
Published Date
2023/4/3
Professor FAQs
What is Sergio Grinstein's h-index at University of Toronto?
The h-index of Sergio Grinstein has been 63 since 2020 and 143 in total.
What are Sergio Grinstein's top articles?
The articles with the titles of
Reactive oxygen species suppress phagocyte surveillance by oxidizing cytoskeletal regulators
Redistribution of the glycocalyx exposes phagocytic determinants on apoptotic cells
Adenomatous polyposis coli (APC) regulates internalization and signaling of the chemorepellent receptor, Roundabout (ROBO) 1
Salmonella exploits membrane reservoirs for invasion of host cells
Target lysis by cholesterol extraction is a rate limiting step in the resolution of phagolysosomes
Destructive breakdown studies of irradiated LGADs at beam tests for the ATLAS HGTD
Lipid peroxidation increases membrane tension, Piezo1 gating, and cation permeability to execute ferroptosis
ClC-7 drives intraphagosomal chloride accumulation to support hydrolase activity and phagosome resolution
...
are the top articles of Sergio Grinstein at University of Toronto.
What are Sergio Grinstein's research interests?
The research interests of Sergio Grinstein are: cell biology, membranes
What is Sergio Grinstein's total number of citations?
Sergio Grinstein has 76,026 citations in total.