期刊
JOURNAL OF CELL SCIENCE
卷 126, 期 9, 页码 1962-1968出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.117374
关键词
SDF2L1; ER stress; ER associated degradation; ERAD; Insulin; Proinsulin; Pancreatic beta-cells
类别
资金
- Natural Sciences and Engineering Research Council of Canada (NSERC) [326823-2009]
- Canadian Institutes of Health Research [MOP102588]
- Banting and Best Diabetes Centre, University of Toronto
- Canada Research Chair in Diabetes Research
Stromal cell-derived factor 2-like 1 (SDF2L1) is an endoplasmic reticulum (ER)-localized protein whose function is undefined. Here we show that SDF2L1 protein levels are increased in response to ER stress-inducing compounds, but not other cell stressors that we tested in insulinoma cell lines. SDF2L1 protein levels were also induced by expression of misfolded proinsulin in insulinoma cells and in islets from diabetic mice. Immunoprecipitation and binding assays demonstrated that SDF2L1 interacts with the ER chaperone GRP78/BiP, the ER-associated degradation (ERAD) machinery and with misfolded proinsulin. Unexpectedly, knockdown of SDF2L1 in INS-1 (insulin 2 C96Y-GFP) cells increased the degradation kinetics of mutant proinsulin, suggesting that SDF2L1 regulates substrate availability for the ERAD system. We suggest that SDF2L1 increases the time that misfolded proteins have to achieve a correctly folded conformation and thus that SDF2L1 can act as a buffer for substrate availability for ERAD in pancreatic beta-cells.
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