title: GTPase of the Immune-Associated Nucleotide Protein 5 Regulates the Lysosomal Calcium Compartment in T Lymphocytes.
abstract: T lymphocytes fromGimap5lyp/lyprats carrying a recessive mutation in the GTPase of immune-associated protein 5 (Gimap5) gene undergo spontaneous apoptosis. Molecular mechanisms underlying this survival defect are not yet clear. We have shown thatGimap5lyp/lypT lymphocytes display reduced calcium influx following T cell antigen receptor (TCR) stimulation that was associated with impaired buffering of calcium by mitochondria. Here, we investigated the subcellular localization of GIMAP5 and its influence on Ca2+response in HEK293T cells and T lymphocytes. The more abundantly expressed GIMAP5v2 localizes to the lysosome and certain endosomal vesicles.Gimap5lyp/lypT lymphocytes showed increased accumulation of calcium in the lysosomes as evidenced by Gly-Phe β-naphthylamide (GPN) triggered Ca2+release. As a corollary, GPN-induced Ca2+flux was decreased in HEK293T cells expressing GIMAP5v2. Strikingly, TCR stimulation of rat, mouse, and human T lymphocytes increased lysosomal calcium content. Overall, our findings show that lysosomes modulate cellular Ca2+response during T cell activation and that GIMAP5 regulates the lysosomal Ca2+compartment in T lymphocytes.
authors.affiliation: Immunology Division, Department of Pediatrics, Université de Sherbrooke , Sherbrooke, QC , Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Serrano
authors.affiliation: Immunology Division, Department of Pediatrics, Université de Sherbrooke , Sherbrooke, QC , Canada.
authors.forename: Farnaz
authors.initials: F
authors.lastname: Ghobadi
authors.affiliation: Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada; Centre de recherche clinique, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Guylain
authors.initials: G
authors.lastname: Boulay
authors.affiliation: Immunology Division, Department of Pediatrics, Université de Sherbrooke, Sherbrooke, QC, Canada; Centre de recherche clinique, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Subburaj
authors.initials: S
authors.lastname: Ilangumaran
authors.affiliation: Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada; Centre de recherche clinique, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Lavoie
authors.affiliation: Immunology Division, Department of Pediatrics, Université de Sherbrooke, Sherbrooke, QC, Canada; Centre de recherche clinique, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Sheela
authors.initials: S
authors.lastname: Ramanathan
keywords: GIMAP5; T cells; calcium; lyp mutation; lysosomes