Assembly of Trp1 in a signaling complex associated with caveolin-scaffolding lipid raft domains.

摘要: Trp1 has been proposed as a component of the store-operated Ca2+ entry (SOC) channel. However, neither molecular mechanism SOC nor role Trp in this process is yet understood. We have examined possible interactions involved regulation and report here for first time that assembled signaling complex associated with caveolin-scaffolding lipid raft domains. Endogenous hTrp1 caveolin-1 were present low density fractions Triton X-100-extracted human submandibular gland cell membranes. Depletion plasma membrane cholesterol increased X-100 solubility inhibited carbachol-stimulated signaling. Importantly, thapsigargin stimulated influx, but not internal release, inositol 1,4,5-triphosphate (IP3)-stimulated I soc also attenuated. Furthermore, both anti-Trp1 anti-caveolin-1 antibodies co-immunoprecipitated hTrp1, caveolin-1, Gαq/11, IP3 receptor-type 3 (IP3R3). These results demonstrate caveolar microdomains provide scaffold (i) assembly key proteins into (ii) coordination leading to activation SOC. we shown localized microdomain where it interacts one or more components complex, including IP3R3. This finding potentially important elucidating physiological function Trp.