Plasma membrane localization of TRPC channels: role of caveolar lipid rafts.
GPCR-mediated activation of the Ca2+ signalling cascade leads to stimulation of Ca2+ influx into non-excitable cells. Both store-dependent and independent channels likely contribute towards this Ca2+ influx. However, the identity of the channels and exact mechanism by which they are activated remains elusive. The TRPC family of proteins has been proposed as molecular components of these channels. Studies from our laboratory and others have shown that mammalian TRPC proteins are assembled in a multiprotein complex that includes various key Ca2+ signalling proteins. However, relatively little is known regarding the mechanisms involved in the assembly of the TRPC channel complex in the plasma membrane. We have reported that TRPC1 and TRPC3 signalling complexes are associated with caveolar lipid raft domains (LRDs) in the plasma membrane. Recently we have examined the role of caveolin-1 in the regulation of TRPC channels and store-operated Ca2+ entry (SOCE). Based on our studies, we suggest that (1) caveolin 1 has a potentially critical role in the localization of TRPC channels plasma membrane caveolar LRDs, and (2) the molecular architecture of caveolae can facilitate intramolecular interactions between TRPC channels and associated proteins that are involved in activation and/or inactivation of SOCE.
Ambudkar
Indu S
IS
Secretory Physiology Section, Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
Brazer
So-ching
SC
Liu
Xibao
X
Lockwich
Timothy
T
Singh
Brij
B
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D022461:Caveolins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D021381:Protein Transport; D050052:TRPC Cation Channels
D015220:Calcium Channels; D022461:Caveolins; D007473:Ion Channels; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C096351:transient receptor potential cation channel, subfamily C, member 1; D002118:Calcium