PMID- 21191072
OWN - NLM
STAT- MEDLINE
DCOM- 20110307
LR  - 20211020
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 186
IP  - 3
DP  - 2011 Feb 1
TI  - Autophagy regulates endoplasmic reticulum homeostasis and calcium mobilization in 
      T lymphocytes.
PG  - 1564-74
LID - 10.4049/jimmunol.1001822 [doi]
AB  - Macroautophagy (hereafter referred to as autophagy) is an evolutionarily 
      conserved intracellular bulk degradation pathway that plays critical roles in 
      eliminating intracellular pathogens, presenting endogenous Ags, and regulating T 
      lymphocyte survival and proliferation. In this study, we have investigated the 
      role of autophagy in regulating the endoplasmic reticulum (ER) compartment in T 
      lymphocytes. We found that ER content is expanded in mature autophagy-related 
      protein (Atg) 7-deficient T lymphocytes. Atg7-deficient T cells stimulated 
      through the TCR display impaired influx, but not efflux, of calcium, and ER 
      calcium stores are increased in Atg7-deficient T cells. Treatment with the ER 
      sarco/ER Ca(2+)-ATPase pump inhibitor thapsigargin rescues the calcium influx 
      defect in Atg7-deficient T lymphocytes, suggesting that this impairment is caused 
      by an intrinsic defect in ER. Furthermore, we found that the stimulation-induced 
      redistribution of stromal interaction molecule-1, a critical event for the 
      store-operated Ca(2+) release-activated Ca(2+) channel opening, is impaired in 
      Atg7-deficient T cells. Together, these findings indicate that the expanded ER 
      compartment in Atg7-deficient T cells contains increased calcium stores, and the 
      inability of these stores to be depleted causes defective calcium influx in these 
      cells. Our results demonstrate that autophagy plays an important role in 
      maintaining ER and calcium homeostasis in T lymphocytes.
FAU - Jia, Wei
AU  - Jia W
AD  - Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
FAU - Pua, Heather H
AU  - Pua HH
FAU - Li, Qi-Jing
AU  - Li QJ
FAU - He, You-Wen
AU  - He YW
LA  - eng
GR  - R01 AI074754/AI/NIAID NIH HHS/United States
GR  - R01 AI074944/AI/NIAID NIH HHS/United States
GR  - AI074754/AI/NIAID NIH HHS/United States
GR  - R01 AI074944-04/AI/NIAID NIH HHS/United States
GR  - R01 AI074944-03/AI/NIAID NIH HHS/United States
GR  - AI074944/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20101229
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Atg7 protein, mouse)
RN  - 0 (Calcium Channels)
RN  - 0 (Microtubule-Associated Proteins)
RN  - EC 6.2.1.45 (Autophagy-Related Protein 7)
SB  - IM
MH  - Animals
MH  - Autophagy/*immunology
MH  - Autophagy-Related Protein 7
MH  - CD4-Positive T-Lymphocytes/cytology/immunology/metabolism
MH  - Calcium Channels/metabolism
MH  - Calcium Signaling/*immunology
MH  - Cell Differentiation/immunology
MH  - Endoplasmic Reticulum/*immunology/metabolism
MH  - Flow Cytometry
MH  - Gene Expression Regulation, Developmental/immunology
MH  - Homeostasis/*immunology
MH  - Intracellular Fluid/immunology/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Microtubule-Associated Proteins/deficiency/genetics/metabolism
MH  - Mitochondria/immunology/metabolism
MH  - Stress, Physiological/immunology
MH  - T-Lymphocyte Subsets/cytology/*immunology/*metabolism
PMC - PMC3285458
MID - NIHMS337916
COIS- Conflict of interest: The authors declare no financial or commercial conflict of 
      interest.
EDAT- 2010/12/31 06:00
MHDA- 2011/03/08 06:00
PMCR- 2012/02/23
CRDT- 2010/12/31 06:00
PHST- 2010/12/31 06:00 [entrez]
PHST- 2010/12/31 06:00 [pubmed]
PHST- 2011/03/08 06:00 [medline]
PHST- 2012/02/23 00:00 [pmc-release]
AID - jimmunol.1001822 [pii]
AID - 10.4049/jimmunol.1001822 [doi]
PST - ppublish
SO  - J Immunol. 2011 Feb 1;186(3):1564-74. doi: 10.4049/jimmunol.1001822. Epub 2010 
      Dec 29.