title: Role of TRPC Channels in Store-Operated Calcium Entry.
abstract: Store-operated calcium entry (SOCE) is a ubiquitous Ca(2+) entry pathway that is activated in response to depletion of Ca(2+) stores within the endoplasmic reticulum (ER) and contributes to the control of various physiological functions in a wide variety of cell types. The transient receptor potential canonical (TRPC) channels (TRPCs 1-7), that are activated by stimuli leading to PIP2 hydrolysis, were first identified as molecular components of SOCE channels. TRPC channels show a miscellany of tissue expression, physiological functions and channel properties. However, none of the TRPC members display currents that resemble I CRAC. Intensive search for the CRAC channel component led to identification of Orai1 and STIM1, now established as being the primary constituents of the CRAC channel. There is now considerable evidence that STIM1 activates both Orai1 and TRPC1 via distinct domains in its C-terminus. Intriguingly, TRPC1 function is not only dependent on STIM1 but also requires Orai1. The critical functional interaction between TRPC1 and Orai1, which determines the activation of TRPC1, has also been identified. In this review, we will discuss current concepts regarding the role of TRPC channels in SOCE, the physiological functions regulated by TRPC-mediated SOCE, and the complex mechanisms underlying the regulation of TRPCs, including the functional interactions with Orai1 and STIM1.
authors.affiliation: Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 10, Room 1N-113, NIH, Bethesda, MD, 20892, USA. ongh@mail.nih.gov.
authors.forename: Hwei Ling
authors.initials: HL
authors.lastname: Ong
authors.affiliation: Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 10, Room 1N-113, NIH, Bethesda, MD, 20892, USA.
authors.forename: Lorena Brito
authors.initials: LB
authors.lastname: de Souza
authors.affiliation: Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 10, Room 1N-113, NIH, Bethesda, MD, 20892, USA. indu.ambudkar@nih.gov.
authors.forename: Indu S
authors.initials: IS
authors.lastname: Ambudkar
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D008565:Membrane Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D050052:TRPC Cation Channels / Q000378:metabolism / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C103530:STIM1 protein, human; C513279:STIM2 protein, human; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D050052:TRPC Cation Channels; D002118:Calcium
keywords: Function; SOCE; TRPC channels; Trafficking