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- Title
CHOP Mediates Endoplasmic Reticulum Stress-Induced Apoptosis in Gimap5-Deficient T Cells.
- Authors
Pino, Steven C.; O'Sullivan-Murphy, Bryan; Lidstone, Erich A.; Chaoxing Yang; Lipson, Kathryn L.; Jurczyk, Agata; diIorio, Philip; Brehm, Michael A.; Mordes, John P.; Greiner, Dale L.; Rossini, Aldo A.; Bortell, Rita
- Abstract
Gimap5 (GTPase of the immunity-associated protein 5) has been linked to the regulation of T cell survival, and polymorphisms in the human GIMAP5 gene associate with autoimmune disorders. The BioBreeding diabetes-prone (BBDP) rat has a mutation in the Gimap5 gene that leads to spontaneous apoptosis of peripheral T cells by an unknown mechanism. Because Gimap5 localizes to the endoplasmic reticulum (ER), we hypothesized that absence of functional Gimap5 protein initiates T cell death through disruptions in ER homeostasis. We observed increases in ER stress-associated chaperones in T cells but not thymocytes or B cells from Gimap5-/- BBDP rats. We then discovered that ER stress-induced apoptotic signaling through C/EBP-homologous protein (CHOP) occurs in Gimap5-/- T cells. Knockdown of CHOP by siRNA protected Gimap5-/- T cells from ER stress-induced apoptosis, thereby identifying a role for this cellular pathway in the T cell lymphopenia of the BBDP rat. These findings indicate a direct relationship between Gimap5 and the maintenance of ER homeostasis in the survival of T cells.
- Subjects
T cells; LYMPHOCYTES; ENDOPLASMIC reticulum; ORGANELLES; GENETIC polymorphisms; HOMEOSTASIS; GUANOSINE triphosphatase; B cells; POLYMORPHISM (Zoology)
- Publication
PLoS ONE, 2009, Vol 4, Issue 5, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0005468