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

Abstract

Store-operated Ca ²⁺ entry is mediated by Ca ²⁺ release–activated Ca ²⁺ (CRAC) channels following Ca ²⁺ release from intracellular stores. We performed a genome-wide RNA interference (RNAi) screen in Drosophila cells to identify proteins that inhibit store-operated Ca ²⁺ 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.