Multiple types of calcium channels arising from alternative translation initiation of the Orai1 message

Pooja N. Desai, Xuexin Zhang, Shilan Wu, Agnes Janoshazi, Sunitha Bolimuntha, James W. Putney, Mohamed Trebak

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

In mammals exclusively, the pore-forming Ca2+ release-activated Ca2+ (CRAC) channel subunit Orai1 occurs in two forms because of alternative translation initiation. The longer, mammal-specific Orai1a contains an additional 63 amino acids upstream of the conserved start site for Orai1b, which occurs at methionine 64 in Orai1a. Orai1 participates in the generation of three distinct Ca2+ currents, including two store-operated currents: Icrac, which involves activation of Orai1 channels by the Ca2+-sensing protein STIM1 (stromal interaction molecule 1), and Isoc, which involves an interaction among Orai1, the transient receptor potential (TRP) family member TRPC1 (TRP canonical 1), and STIM1. Orai1 is also a pore-forming subunit of an arachidonic acid (or leukotriene C4)-regulated current Iarc that involves interactions among Orai1, Orai3, and STIM1. We evaluated the roles of the two Orai1 forms in the Ca2+ currents Icrac, Isoc, and Iarc. We found that Orai1a and Orai1b were largely interchangeable for Icrac and Isoc, although Orai1a exhibited stronger inhibition by Ca2+. Only the mammalian-specific Orai1a functioned in the arachidonic acid-regulated current Iarc. Thus, alternative translation initiation of the Orai1 message produces at least three types of Ca2+ channels with distinct signaling and regulatory properties.

Original languageEnglish (US)
Article numberra74
JournalScience signaling
Volume8
Issue number387
DOIs
StatePublished - Jul 28 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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