Autophagy, a novel pathway to regulate calcium mobilization in T lymphocytes

Journal Article (Review;Journal)

The T lymphocyte response initiates with the recognition of MHC/peptides on antigen presenting cells by the T cell receptor (TCR). After the TCR engagement, the proximal signaling 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 in T cell proliferation, cell survival, and apoptosis. In studying the roles of macroautophagy (hereafter referred to as autophagy) in T cell function, 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 in T 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 calcium 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. © 2013 Jia, He, McLeod and He.

Full Text

Duke Authors

Cited Authors

  • Jia, W; He, MX; McLeod, IX; He, YW

Published Date

  • September 16, 2013

Published In

Volume / Issue

  • 4 / JUL

Electronic International Standard Serial Number (EISSN)

  • 1664-3224

Digital Object Identifier (DOI)

  • 10.3389/fimmu.2013.00179

Citation Source

  • Scopus