CRACM1 Is a Plasma Membrane Protein Essential for Store-Operated Ca ²⁺ Entry

TLDR

Store‑operated Ca²⁺ entry is mediated by CRAC channels after Ca²⁺ release from intracellular stores, and CRACM1 may represent the channel itself, a subunit, or a component of its signaling machinery. The authors performed a genome‑wide RNAi screen in Drosophila cells to identify proteins that inhibit store‑operated Ca²⁺ influx and then characterized the human ortholog of CRACM1, a plasma‑membrane protein encoded by FLJ14466. Patch‑clamp screening revealed that CRACM1 and CRACM2 modulate Drosophila CRAC currents, and while CRACM1 overexpression had no effect, its knockdown via RNAi disrupted channel activation.

Abstract

Store-operated Ca2+ entry is mediated by Ca2+ release-activated Ca2+ (CRAC) channels following Ca2+ release from intracellular stores. We performed a genome-wide RNA interference (RNAi) screen in Drosophila cells to identify proteins that inhibit store-operated Ca2+ influx. A secondary patch-clamp screen identified CRACM1 and CRACM2 (CRAC modulators 1 and 2) as modulators of Drosophila CRAC currents. We characterized the human ortholog of CRACM1, a plasma membrane-resident protein encoded by gene FLJ14466. Although overexpression of CRACM1 did not affect CRAC currents, RNAi-mediated knockdown disrupted its activation. CRACM1 could be the CRAC channel itself, a subunit of it, or a component of the CRAC signaling machinery.