Calmodulin Regulates Ca2+-sensing Receptor-mediated Ca2+ Signaling and Its Cell Surface Expression |
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| Authors: | Yun Huang Yubin Zhou Hing-Cheung Wong Adriana Castiblanco Yanyi Chen Edward M. Brown Jenny J. Yang |
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| Affiliation: | From the ‡Department of Chemistry, Center for Drug Design and Advanced Biotechnology, Georgia State University, Atlanta, Georgia 30303 and ;the §Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women''s Hospital, Boston, Massachusetts 02115 |
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| Abstract: | The Ca2+-sensing receptor (CaSR) is a member of family C of the GPCRs responsible for sensing extracellular Ca2+ ([Ca2+]o) levels, maintaining extracellular Ca2+ homeostasis, and transducing Ca2+ signaling from the extracellular milieu to the intracellular environment. In the present study, we have demonstrated a Ca2+-dependent, stoichiometric interaction between CaM and a CaM-binding domain (CaMBD) located within the C terminus of CaSR (residues 871–898). Our studies suggest a wrapping around 1–14-like mode of interaction that involves global conformational changes in both lobes of CaM with concomitant formation of a helical structure in the CaMBD. More importantly, the Ca2+-dependent association between CaM and the C terminus of CaSR is critical for maintaining proper responsiveness of intracellular Ca2+ responses to changes in extracellular Ca2+ and regulating cell surface expression of the receptor. |
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| Keywords: | Calcium Calmodulin Cell Surface Receptor Protein-Protein Interactions Receptors Signal Transduction Trafficking Calcium-sensing Receptor Surface Expression |
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