Ca2+ release-activated Ca2+ (CRAC) current, structure, and function

Store-operated Ca2+ entry describes the phenomenon that connects a depletion of internal Ca2+ stores to an activation of plasma membrane-located Ca2+ selective ion channels. Tremendous progress towards the underlying molecular mechanism came with the discovery of the two respective limiting components, STIM and Orai. STIM1 represents the ER-located Ca2+ sensor and transmits the signal of store depletion to the plasma membrane. Here it couples to and activates Orai, the highly Ca2+-selective pore-forming subunit of Ca2+ release-activated Ca2+ channels. In this review, we focus on the molecular steps that these two proteins undergo from store-depletion to their coupling, the activation, and regulation of Ca2+ currents.