Seraf, A Novel Regulator Of Store Operated Calcium Entry

Store operated calcium entry (SOCE) is a principal cellular process by which cells regulate basal calcium, refill intracellular calcium stores and execute a wide range of specialized activities. In recent years tremendous progress has been made in understanding the nature of the molecular components and events that govern SOCE activation. STIM and Orai were identified as the essential components able to reconstitute Ca2+ release-activated Ca2+ (CRAC) channels that mediate SOCE. Here, we report the molecular identification of SERAF, a novel regulator of SOCE. Using heterologous expression, RNAi-mediated silencing and site directed mutagenesis, combined with electrophysiological, biochemical and imaging techniques; we show that SERAF is an endoplasmic reticulum membrane protein that associates with STIM to facilitate SOCE inactivation following calcium refilling. SERAF, therefore, plays a key role in shaping cytosolic Ca2+ signals and determining the content of the major intracellular calcium stores, role that is likely to be important for protecting cells from calcium overfilling.