Secretagogin Is a Redox-Responsive Ca2+ Sensor

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• 作者：Radhika Khandelwal ; Anand Kumar Sharma ; Swathi Chadalawada ; Yogendra Sharma
• 刊名：Biochemistry
• 出版年：2017
• 出版时间：January 17, 2017
• 年：2017
• 卷：56
• 期：2
• 页码：411-420
• 全文大小：719K
• ISSN：1520-4995

文摘

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.