title: Loss of GIMAP5 (GTPase of immunity-associated nucleotide binding protein 5) impairs calcium signaling in rat T lymphocytes.
abstract: The recessive lyp allele, which harbors a defective gimap5 (GTPase of immunity-associated nucleotide binding protein 5) gene, causes spontaneous apoptosis of T lymphocytes in the biobreeding diabetes-prone strain of rats. Mechanisms underlying the pro-survival function of GIMAP5 remain unclear. In this study, we show that gimap5(lyp/lyp) T cells display diminished calcium flux in response to thapsigargin or signaling via the T cell antigen receptor. This defect is manifested in mature single positive thymocytes, where the survival defect first occurs. We also show that GIMAP5 deficiency does not affect the thapsigargin-induced calcium release from the intracellular stores but impairs subsequent calcium entry across the plasma membrane. Our findings suggest that GIMAP5 is an important regulator of calcium response in T lymphocytes and impaired calcium signaling might underlie spontaneous apoptosis of gimap5(lyp/lyp) T cells.
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, University of Sherbrooke, Québec, Canada.
authors.forename: Subburaj
authors.initials: S
authors.lastname: Ilangumaran
authors.forename: Melissa
authors.initials: M
authors.lastname: Forand-Boulerice
authors.forename: Simon M
authors.initials: SM
authors.lastname: Bousquet
authors.forename: Alexandre
authors.initials: A
authors.lastname: Savard
authors.forename: Philippe
authors.initials: P
authors.lastname: Rocheleau
authors.forename: Xi Lin
authors.initials: XL
authors.lastname: Chen
authors.forename: Gilles
authors.initials: G
authors.lastname: Dupuis
authors.forename: Philippe
authors.initials: P
authors.lastname: Poussier
authors.forename: Guylain
authors.initials: G
authors.lastname: Boulay
authors.forename: Sheela
authors.initials: S
authors.lastname: Ramanathan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D020013:Calcium Signaling / Q000276:immunology* / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology*; D066298:In Vitro Techniques; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019284:Thapsigargin / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology
chemical_list: D011948:Receptors, Antigen, T-Cell; D019284:Thapsigargin; D019204:GTP-Binding Proteins; C494977:Gimap5 protein, rat