title: Secretagogin Is a Redox-Responsive Ca2+Sensor.
abstract: 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.
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology (CCMB) , Uppal Road, Hyderabad 500 007, India.|Academy of Scientific and Innovative Research (AcSIR) , New Delhi, India.
authors.forename: Radhika
authors.initials: R
authors.lastname: Khandelwal
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology (CCMB) , Uppal Road, Hyderabad 500 007, India.
authors.forename: Anand Kumar
authors.initials: AK
authors.lastname: Sharma
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology (CCMB) , Uppal Road, Hyderabad 500 007, India.
authors.forename: Swathi
authors.initials: S
authors.lastname: Chadalawada
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology (CCMB) , Uppal Road, Hyderabad 500 007, India.|Academy of Scientific and Innovative Research (AcSIR) , New Delhi, India.
authors.forename: Yogendra
authors.identifier: http://orcid.org/0000-0003-1345-8478
authors.initials: Y
authors.lastname: Sharma
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003001:Cloning, Molecular; D003545:Cysteine / Q000737:chemistry* / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011485:Protein Binding; D000072417:Protein Domains; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D064046:Secretagogins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; C576557:SCGN protein, mouse; D064046:Secretagogins; D003545:Cysteine; D002118:Calcium; D004229:Dithiothreitol