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The TRPCs–STIM1–Orai Interaction

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Mammalian Transient Receptor Potential (TRP) Cation Channels

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 223))

Abstract

Ca2+ signaling entails receptor-stimulated Ca2+ release from the ER stores that serves as a signal to activate Ca2+ influx channels present at the plasma membrane, the store-operated Ca2+ channels (SOCs). The two known SOCs are the Orai and TRPC channels. The SOC-dependent Ca2+ influx mediates and sustains virtually all Ca2+-dependent regulatory functions. The signal that transmits the Ca2+ content of the ER stores to the plasma membrane is the ER resident, Ca2+-binding protein STIM1. STIM1 is a multidomain protein that clusters and dimerizes in response to Ca2+ store depletion leading to activation of Orai and TRPC channels. Activation of the Orais by STIM1 is obligatory for their function as SOCs, while TRPC channels can function as both STIM1-dependent and STIM1-independent channels. Here we discuss the different mechanisms by which STIM1 activates the Orai and TRPC channels, the emerging specific and non-overlapping physiological functions of Ca2+ influx mediated by the two channel types, and argue that the TRPC channels should be the preferred therapeutic target to control the toxic effect of excess Ca2+ influx.

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Authors and Affiliations

  1. Epithelial Signaling and Transport Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, MD, 20892, USA

    Seok Choi, Jozsef Maleth, Archana Jha & Malini Ahuja

  2. Department of Physiology, College of Veterinary Medicine, Chungnam National University, Daejeon, 305-764, Republic of Korea

    Kyu Pil Lee

  3. Department of Oral Physiology, School of Dentistry, Wonkwang University, Iksan City, Jeonbuk, Republic of Korea

    Min Seuk Kim

  4. Department of Physiology and Biophysics, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea

    Insuk So

  5. Epithelial Signaling and Transport Section, Molecular Physiology and Therapeutics Branch, NIDCR, NIH, Building 10, Room 1N-112, Bethesda, MD, 20892, USA

    Shmuel Muallem

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  1. Seok Choi
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Correspondence to Shmuel Muallem .

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Editors and Affiliations

  1. Laboratory Ion Channel Research, Campus Gasthuisberg, KU Leuven Department, Cell Mol Medicin, Leuven, Belgium

    Bernd Nilius

  2. Pharmakologie und Toxikologie, Universität des Saarlandes, Institut für Experimentelle u. Klinische, Homburg, Germany

    Veit Flockerzi

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Choi, S. et al. (2014). The TRPCs–STIM1–Orai Interaction. In: Nilius, B., Flockerzi, V. (eds) Mammalian Transient Receptor Potential (TRP) Cation Channels. Handbook of Experimental Pharmacology, vol 223. Springer, Cham. https://doi.org/10.1007/978-3-319-05161-1_13

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