| First Author | Desai PN | Year | 2015 |
| Journal | Sci Signal | Volume | 8 |
| Issue | 387 | Pages | ra74 |
| PubMed ID | 26221052 | Mgi Jnum | J:260186 |
| Mgi Id | MGI:6142525 | Doi | 10.1126/scisignal.aaa8323 |
| Citation | Desai PN, et al. (2015) Multiple types of calcium channels arising from alternative translation initiation of the Orai1 message. Sci Signal 8(387):ra74 |
| abstractText | In mammals exclusively, the pore-forming Ca(2+) release-activated Ca(2+) (CRAC) channel subunit Orai1 occurs in two forms because of alternative translation initiation. The longer, mammal-specific Orai1alpha contains an additional 63 amino acids upstream of the conserved start site for Orai1beta, which occurs at methionine 64 in Orai1alpha. Orai1 participates in the generation of three distinct Ca(2+) currents, including two store-operated currents: Icrac, which involves activation of Orai1 channels by the Ca(2+)-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 Ca(2+) currents Icrac, Isoc, and Iarc. We found that Orai1alpha and Orai1beta were largely interchangeable for Icrac and Isoc, although Orai1alpha exhibited stronger inhibition by Ca(2+). Only the mammalian-specific Orai1alpha functioned in the arachidonic acid-regulated current Iarc. Thus, alternative translation initiation of the Orai1 message produces at least three types of Ca(2+) channels with distinct signaling and regulatory properties. |
