Orai1 is a novel ciliary Ca2+ channel involved in the ciliary formation and SHH signaling, which maintains the Left-Right asymmetry

Abstract

Cilia are essential cellular structures crucial for sensing and transmitting external signals and aiding in development. They contain higher calcium ions (Ca2+) levels than the surrounding cytosol. Although some Ca2+ channels like PC2, TMPR4, and TRPP2 are known, the precise pathway remains unclear. Our research reveals that SOCE, a recognized calcium pathway in intracellular signaling, contributes to cilia calcium supply. The study highlights Orai1, a SOCE component, as vital for ciliogenesis and ciliary signaling. Disrupted Orai1 function reduces cilia frequency and length in RPE-1 cells. SOCE activation increases SHH pathway activity, while inhibition diminishes it in NIH-3T3 cells. Defective SOCE-induced cilia reduction occurs in Xenopus and disrupts embryonic LR asymmetry. This discovery identifies Orai1 as a novel Ca2+ channel essential for ciliogenesis, ciliary SHH signaling, and development. It holds promise for investigating Ca2+-dependent ciliopathies—disorders due to cilia structure/function issues.