Calmodulin regulates Ca2+-sensing receptor-mediated Ca2+ signaling and its cell surface expression.
The Ca(2+)-sensing receptor (CaSR) is a member of family C of the GPCRs responsible for sensing extracellular Ca(2+) ([Ca(2+)](o)) levels, maintaining extracellular Ca(2+) homeostasis, and transducing Ca(2+) signaling from the extracellular milieu to the intracellular environment. In the present study, we have demonstrated a Ca(2+)-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 Ca(2+)-dependent association between CaM and the C terminus of CaSR is critical for maintaining proper responsiveness of intracellular Ca(2+) responses to changes in extracellular Ca(2+) and regulating cell surface expression of the receptor.
Huang
Yun
Y
Department of Chemistry, Center for Drug Design and Advanced Biotechnology, Georgia State University, Atlanta, Georgia 30303, USA.
Zhou
Yubin
Y
Wong
Hing-Cheung
HC
Castiblanco
Adriana
A
Chen
Yanyi
Y
Brown
Edward M
EM
Yang
Jenny J
JJ
D000465:Algorithms; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002147:Calmodulin / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002942:Circular Dichroism; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D042541:Intracellular Space / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D002147:Calmodulin; D044169:Receptors, Calcium-Sensing; D002118:Calcium
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