Calmodulin regulates Ca(2+)-dependent feedback inhibition of store-operated Ca(2+) influx by interaction with a site in the C terminus of TrpC1

Brij B Singh; Xibao Liu; Jisen Tang; Michael X Zhu; Indu S Ambudkar

doi:10.1016/s1097-2765(02)00506-3

Calmodulin regulates Ca(2+)-dependent feedback inhibition of store-operated Ca(2+) influx by interaction with a site in the C terminus of TrpC1

Mol Cell. 2002 Apr;9(4):739-50. doi: 10.1016/s1097-2765(02)00506-3.

Authors

Brij B Singh¹, Xibao Liu, Jisen Tang, Michael X Zhu, Indu S Ambudkar

Affiliation

¹ Secretory Physiology Section, Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.

PMID: 11983166
DOI: 10.1016/s1097-2765(02)00506-3

Abstract

The mechanism involved in [Ca(2+)](i)-dependent feedback inhibition of store-operated Ca(2+) entry (SOCE) is not yet known. Expression of Ca(2+)-insensitive calmodulin (Mut-CaM) but not wild-type CaM increased SOCE and decreased its Ca(2+)-dependent inactivation. Expression of TrpC1 lacking C terminus aa 664-793 (TrpC1DeltaC) also attenuated Ca(2+)-dependent inactivation of SOCE. CaM interacted with endogenous and expressed TrpC1 and with GST-TrpC1 C terminus but not with TrpC1DeltaC. Two CaM binding domains, aa 715-749 and aa 758-793, were identified. Expression of TrpC1Delta758-793 but not TrpC1Delta715-749 mimicked the effects of TrpC1DeltaC and Mut-CaM on SOCE. These data demonstrate that CaM mediates Ca(2+)-dependent feedback inhibition of SOCE via binding to a domain in the C terminus of TrpC1. These findings reveal an integral role for TrpC1 in the regulation of SOCE.

MeSH terms

Amino Acid Substitution
Binding Sites
Calcium Channels / chemistry
Calcium Channels / metabolism*
Calcium Channels / physiology
Calcium Signaling / physiology*
Calmodulin / chemistry
Calmodulin / genetics
Calmodulin / physiology*
Cell Compartmentation
Cell Line / drug effects
Cell Line / metabolism
DNA, Complementary / genetics
Epithelial Cells / drug effects
Epithelial Cells / metabolism
Feedback
Humans
Ion Channel Gating / physiology
Ion Transport / physiology
Mutagenesis, Site-Directed
Patch-Clamp Techniques
Peptide Fragments / metabolism
Protein Binding
Protein Interaction Mapping
Protein Structure, Tertiary
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / metabolism
Sequence Deletion
Submandibular Gland / cytology
TRPC Cation Channels
Transfection

Substances

Calcium Channels
Calmodulin
DNA, Complementary
Peptide Fragments
Recombinant Fusion Proteins
TRPC Cation Channels
transient receptor potential cation channel, subfamily C, member 1