Secretagogin Is a Redox-Responsive Ca2+ Sensor

被引:16
作者
Khandelwal, Radhika [1 ,2 ]
Sharma, Anand Kumar [1 ]
Chadalawada, Swathi [1 ]
Sharma, Yogendra [1 ,2 ]
机构
[1] CSIR, CCMB, Uppal Rd, Hyderabad 500007, Andhra Pradesh, India
[2] AcSIR, New Delhi, India
关键词
ENDOPLASMIC-RETICULUM STRESS; CA2+-BINDING PROTEIN; DISULFIDE BONDS; CALCIUM; STABILITY; BINDING; EXPRESSION; NEURONS; MOUSE; OVEREXPRESSION;
D O I
10.1021/acs.biochem.6b00761
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Secretagogin (SCGN), a multifunctional, Ca2+ binding, regulatory protein, known to regulate insulin release, has recently been implicated in the control of stress-related corticotropin-releasing hormone (CRH) secretion. Localization of SCGN to multiple intracellular (such as cytosol, nucleus, and endoplasmic reticulum) and extracellular sites appears to provide multifunctional capabilities; however, the structural elements conferring such a widespread cellular distribution to SCGN remain unidentified. We report that the spatial and functional attributes of SCGN plausibly originate from the interplay between Ca2+ and its redox state. The mutation of selective Cys residues provides further insights into the origin and mode of redox responsiveness. In the reducing milieu, SCGN exhibits a higher affinity for Ca2+, and more stability than in the oxidizing environment, suggesting it is a redox-responsive Ca2+ sensor protein, which is further supported by its response to dithiothreitol (reducing stress) in MIN6 cells. Our data provide a biophysical and biochemical explanation for the diverse localization of SCGN in the cellular scenario and beyond the cell.
引用
收藏
页码:411 / 420
页数:10
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