High resolution

Module 3: Figure STIM-induced Ca2+ entry

Proposed function of stromal interaction molecule (STIM) in store-operated Ca2+ entry in T cells.

The top panels illustrate how the entry of Ca2+ depends upon activation of a store-operated channel such as Orai1. When the store empties, the stromal interaction molecule 1 (STIM1) migrates towards regions of the endoplasmic reticulum where it functions to open the Orai1 channels (white box). The models at the bottom show two possible mechanisms for the conformational coupling mechanism. It may occur through a direct interaction between Orai1 and STIM1, perhaps involving the coiled-coil domains (red boxes). Since these proteins are relatively small, such an interaction would require close apposition of the two membranes. Alternatively, STIM1 may exert its effects through an accessory protein such as the inositol 1,4,5-trisphosphate receptor (InsP3R) or through a ryanodine receptor (RYR). Formation of such coupling complexes appear to depend upon cytoskeletal remodelling driven by Wiskott–Aldrich syndrome protein (WASP) verprolin homologous 2 (WAVE2) and controlled through the monomeric G proteins Vav and Rac.