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

作者：Desai Pooja N; Zhang Xuexin; Wu Shilan; Janoshazi Agnes; Bolimuntha Sunitha; Putney James W^*; Trebak Mohamed

来源：Science Signaling, 2015, 8(387): ra74.

DOI：10.1126/scisignal.aaa8323

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 Orai1 alpha contains an additional 63 amino acids upstream of the conserved start site for Orai1 beta, which occurs at methionine 64 in Orai1 alpha. Orai1 participates in the generation of three distinct Ca2+ currents, including two store-operated currents: I-crac, which involves activation of Orai1 channels by the Ca2+-sensing protein STIM1 (stromal interaction molecule 1), and I-soc, 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 C-4)-regulated current I-arc that involves interactions among Orai1, Orai3, and STIM1. We evaluated the roles of the two Orai1 forms in the Ca2+ currents I-crac, I-soc, and I-arc. We found that Orai1 alpha and Orai1 beta were largely interchangeable for I-crac and I-soc, although Orai1 alpha exhibited stronger inhibition by Ca2+. Only the mammalian-specific Orai1 alpha functioned in the arachidonic acid-regulated current I-arc. Thus, alternative translation initiation of the Orai1 message produces at least three types of Ca2+ channels with distinct signaling and regulatory properties.

• 出版日期2015-7-28