Biogenesis of the Store Operated Ca2+ Channel, Orai1

Abstract Background: Ca2+ plays an essential role as a second messenger regulating many cellular functions including gene regulation and enzyme activity. Thus intracellular Ca2+ concentration is tightly regulated. Store operated Ca2+ channel (SOC) is a plasma membrane channel, which is activated upon depletion of endoplasmic reticulum (ER) Ca2+. This channel is compromised of two proteins STIM1, that is localized to the ER membrane and senses luminal Ca2+ concentration, and Orai1, that forms the channel at the plasma membrane. To date little is known about the synthesis and maturation of Orai1 protein. Calreticulin and calnexin are two lectin-like chaperones in the ER, which are involved in the synthesis and maturation of many membrane and secretory proteins. In addition to its chaperone function, calreticulin binds Ca2+ with high capacity and low affinity and regulates intracellular Ca2+ homeostasis. Previously, we showed that loss of calreticulin function activates ER stress pathways leading to the acti...