Amplification of CRAC current by STIM1 and CRACM1 (Orai1)

Depletion of intracellular calcium stores activates store-operated calcium entry across the plasma membrane in many cells. STIM1, the putative calcium sensor in the endoplasmic reticulum, and the calcium release-activated calcium ( CRAC) modulator CRACM1 ( also known as Orai1) in the plasma membrane have recently been shown to be essential for controlling the store-operated CRAC current ( I-CRAC)(1-4). However, individual overexpression of either protein fails to significantly amplify I-CRAC. Here, we show that STIM1 and CRACM1 interact functionally. Overexpression of both proteins greatly potentiates I-CRAC, suggesting that STIM1 and CRACM1 mutually limit store-operated currents and that CRACM1 may be the long-sought CRAC channel.