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STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels.
Nat Cell Biol. 2006 Sep; 8(9):1003-10.NC

Abstract

Receptor-evoked Ca2+ signalling involves Ca2+ release from the endoplasmic reticulum, followed by Ca2+ influx across the plasma membrane. Ca2+ influx is essential for many cellular functions, from secretion to transcription, and is mediated by Ca2+-release activated Ca2+ (I(crac)) channels and store-operated calcium entry (SOC) channels. Although the molecular identity and regulation of I(crac) and SOC channels have not been precisely determined, notable recent findings are the identification of STIM1, which has been indicated to regulate SOC and I(crac) channels by functioning as an endoplasmic reticulum Ca2+ sensor, and ORAI1 (ref. 7) or CRACM1 (ref. 8)--both of which may function as I(crac) channels or as an I(crac) subunit. How STIM1 activates the Ca2+ influx channels and whether STIM1 contributes to the channel pore remains unknown. Here, we identify the structural features that are essential for STIM1-dependent activation of SOC and I(crac) channels, and demonstrate that they are identical to those involved in the binding and activation of TRPC1. Notably, the cytosolic carboxyl terminus of STIM1 is sufficient to activate SOC, I(crac) and TRPC1 channels even when native STIM1 is depleted by small interfering RNA. Activity of STIM1 requires an ERM domain, which mediates the selective binding of STIM1 to TRPC1, 2 and 4, but not to TRPC3, 6 or 7, and a cationic lysine-rich region, which is essential for gating of TRPC1. Deletion of either region in the constitutively active STIM1(D76A) yields dominant-negative mutants that block native SOC channels, expressed TRPC1 in HEK293 cells and I(crac) in Jurkat cells. These observations implicate STIM1 as a key regulator of activity rather than a channel component, and reveal similar regulation of SOC, I(crac) and TRPC channel activation by STIM1.

Authors+Show Affiliations

Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16906149

Citation

Huang, Guo N., et al. "STIM1 Carboxyl-terminus Activates Native SOC, I(crac) and TRPC1 Channels." Nature Cell Biology, vol. 8, no. 9, 2006, pp. 1003-10.
Huang GN, Zeng W, Kim JY, et al. STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels. Nat Cell Biol. 2006;8(9):1003-10.
Huang, G. N., Zeng, W., Kim, J. Y., Yuan, J. P., Han, L., Muallem, S., & Worley, P. F. (2006). STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels. Nature Cell Biology, 8(9), 1003-10.
Huang GN, et al. STIM1 Carboxyl-terminus Activates Native SOC, I(crac) and TRPC1 Channels. Nat Cell Biol. 2006;8(9):1003-10. PubMed PMID: 16906149.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels. AU - Huang,Guo N, AU - Zeng,Weizhong, AU - Kim,Joo Young, AU - Yuan,Joseph P, AU - Han,Linhuang, AU - Muallem,Shmuel, AU - Worley,Paul F, Y1 - 2006/08/13/ PY - 2006/04/12/received PY - 2006/06/12/accepted PY - 2006/8/15/pubmed PY - 2006/10/19/medline PY - 2006/8/15/entrez SP - 1003 EP - 10 JF - Nature cell biology JO - Nat. Cell Biol. VL - 8 IS - 9 N2 - Receptor-evoked Ca2+ signalling involves Ca2+ release from the endoplasmic reticulum, followed by Ca2+ influx across the plasma membrane. Ca2+ influx is essential for many cellular functions, from secretion to transcription, and is mediated by Ca2+-release activated Ca2+ (I(crac)) channels and store-operated calcium entry (SOC) channels. Although the molecular identity and regulation of I(crac) and SOC channels have not been precisely determined, notable recent findings are the identification of STIM1, which has been indicated to regulate SOC and I(crac) channels by functioning as an endoplasmic reticulum Ca2+ sensor, and ORAI1 (ref. 7) or CRACM1 (ref. 8)--both of which may function as I(crac) channels or as an I(crac) subunit. How STIM1 activates the Ca2+ influx channels and whether STIM1 contributes to the channel pore remains unknown. Here, we identify the structural features that are essential for STIM1-dependent activation of SOC and I(crac) channels, and demonstrate that they are identical to those involved in the binding and activation of TRPC1. Notably, the cytosolic carboxyl terminus of STIM1 is sufficient to activate SOC, I(crac) and TRPC1 channels even when native STIM1 is depleted by small interfering RNA. Activity of STIM1 requires an ERM domain, which mediates the selective binding of STIM1 to TRPC1, 2 and 4, but not to TRPC3, 6 or 7, and a cationic lysine-rich region, which is essential for gating of TRPC1. Deletion of either region in the constitutively active STIM1(D76A) yields dominant-negative mutants that block native SOC channels, expressed TRPC1 in HEK293 cells and I(crac) in Jurkat cells. These observations implicate STIM1 as a key regulator of activity rather than a channel component, and reveal similar regulation of SOC, I(crac) and TRPC channel activation by STIM1. SN - 1465-7392 UR - https://www.unboundmedicine.com/medline/citation/16906149/STIM1_carboxyl_terminus_activates_native_SOC_I_crac__and_TRPC1_channels_ L2 - http://dx.doi.org/10.1038/ncb1454 DB - PRIME DP - Unbound Medicine ER -