An endoplasmic reticulum/plasma membrane junction: STIM1/Orai1/TRPCs

Lee, Kyu Pil; Yuan, Joseph P.; Hong, Jeong Hee; So, Insuk; Worley, Paul F.; Muallem, Shmuel

doi:10.1016/j.febslet.2009.11.078

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Volume 584, Issue 10 , Pages 2022-2027, 17 May 2010

An endoplasmic reticulum/plasma membrane junction: STIM1/Orai1/TRPCs

Edited by Wilhelm Just

Kyu Pil Lee
- Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
Joseph P. Yuan
- Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
Jeong Hee Hong
- Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
Insuk So
- Department of Physiology and Biophysics, Seoul National University College of Medicine, Seoul 110-799, Korea
Paul F. Worley
- The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
- Corresponding authors. Addresses: Johns Hopkins School of Medicine, 905 Hunterian Bld., 725 N. Wolfe Street, Baltimore, MD 21205, United States. Fax: +1 410 614 6249 (P.F. Worley), Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9040, United States. Fax: +1 214 645 6049 (S. Muallem).
Shmuel Muallem
- Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
- Corresponding authors. Addresses: Johns Hopkins School of Medicine, 905 Hunterian Bld., 725 N. Wolfe Street, Baltimore, MD 21205, United States. Fax: +1 410 614 6249 (P.F. Worley), Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9040, United States. Fax: +1 214 645 6049 (S. Muallem).

Received 13 November 2009; accepted 22 November 2009. published online 25 November 2009.

Abstract

Ca²⁺ entering cells through store-operated channels (SOCs) affects most cell functions, and excess SOC is associated with pathologies. The molecular makeup of SOCs and their mechanisms of gating were clarified with the discovery of the Orais and STIM1. Another form of SOCs are the TRPCs. STIM1 gates both Orai and TRPC channels but does so by different mechanisms. Although the STIM1 SOAR domain mediates the binding of STIM1 to both channel types, SOAR is sufficient to open the Orais but the STIM1 polylysine domain mediates opening of the TRPC channels. This short review discusses recent findings on how STIM1 gates and regulates the Orais and TRPCs, and how the STIM1/Orai1/TRPCs complexes may function in vivo to mediate SOC activity.

Keywords: Orai, TRPC, Channel, STIM1, Gating