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- Title
Autophagy, a novel pathway to regulate calcium mobilization inT lymphocytes.
- Authors
Wei Jia; Ming-Xiao He; Ian X. McLeod; You-Wen He
- Abstract
The T lymphocyte response initiates with the recognition of MHC/peptides on antigen presenting cells by theT cell receptor (TCR). After the TCR engagement, the proximal sig naling pathways are activated for downstream cellular events. Among these pathways, the calcium-signaling flux is activated through the depletion of endoplasmic reticulum (ER) calcium stores and plays pivotal roles inT cell proliferation, cell survival, and apoptosis. In studying the roles of macroautophagy (hereafter referred to as autophagy) in T cell func tion, we found that a pathway for intracellular degradation, autophagy, regulates calcium signaling by developmentally maintaining the homeostasis of the ER. Using mouse genetic models with specific deletion of autophagy-related genes inT lymphocytes, we found that the calcium influx is defective and the calcium efflux is increased in autophagy-deficient T cells. The abnormal calcium flux is related to the expansion of the ER and higher cal cium stores in the ER. Because of this, treatment with the ER sarco/ER Ca2+-ATPase pump inhibitor, thapsigargin, rescues the calcium influx defect in autophagy-deficient T cells. Therefore, autophagy regulates calcium mobilization in T lymphocytes through ER homeostasis.
- Subjects
AUTOPHAGY; T cell receptors; HOMEOSTASIS; ENDOPLASMIC reticulum; CELL proliferation; ADENOSINE triphosphatase; THAPSIGARGIN
- Publication
Frontiers in Immunology, 2013, Vol 4, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2013.00179