PT - JOURNAL ARTICLE AU - Angela M. Kwiatek AU - Richard D. Minshall AU - David R. Cool AU - Randal A. Skidgel AU - Asrar B. Malik AU - Chinnaswamy Tiruppathi TI - Caveolin-1 Regulates Store-Operated Ca<sup>2+</sup> Influx by Binding of Its Scaffolding Domain to Transient Receptor Potential Channel-1 in Endothelial Cells AID - 10.1124/mol.105.021741 DP - 2006 Oct 01 TA - Molecular Pharmacology PG - 1174--1183 VI - 70 IP - 4 4099 - http://molpharm.aspetjournals.org/content/70/4/1174.short 4100 - http://molpharm.aspetjournals.org/content/70/4/1174.full SO - Mol Pharmacol2006 Oct 01; 70 AB - Caveolin-1 associates with store-operated cation channels (SOC) in endothelial cells. We examined the role of the caveolin-1 scaffolding domain (CSD) in regulating the SOC [i.e., transient receptor potential channel-1 (TRPC1)] in human pulmonary artery endothelial cells (HPAECs). We used the cellpermeant antennapedia (AP)-conjugated CSD peptide, which competes for protein binding partners with caveolin-1, to assess the interactions of caveolin-1 with TRPC1 and its consequences on thrombin-induced Ca2+ influx. We observed that AP-CSD peptide markedly reduced thrombin-induced Ca2+ influx via SOC in HPAECs in contrast to control peptide. AP-CSD also suppressed thapsigargin-induced Ca2+ influx. Streptavidin-bead pull-down assay indicated strong binding of biotin-labeled AP-CSD peptide to TRPC1. Immunoprecipitation studies demonstrated an interaction between endogenous TRPC1 and ectopically expressed hemagglutinin-tagged CSD. Analysis of the deduced TRPC1 amino acid sequence revealed the presence of CSD binding consensus sequence in the TRPC1 C terminus. We also observed that an AP-TRPC1 peptide containing the CSD binding sequence markedly reduced the thrombin-induced Ca2+ influx. We identified the interaction between biotin-labeled AP-TRPC1 C terminus peptide and caveolin-1. Thus, these results demonstrate a crucial role of caveolin-1 scaffolding domain interaction with TRPC1 in regulating Ca2+ influx via SOC. The American Society for Pharmacology and Experimental Therapeutics