Fig. 5.

Models for the proposed actions of STIM1 in the activation of SOCs. (A) Cell at rest with ER stores filled with Ca²⁺. STIM1 molecules (pink) with Ca²⁺ bound are shown predominantly in the ER but also appear in the PM. The SOC (yellow) is closed. (B) Upon Ca²⁺ depletion of the ER, the ER STIM1 proteins become aggregated into puncta, shown as distinct regions of the ER close to the PM. (C) In the “insertional” model, the STIM1 protein is translocated and inserted into the PM. (D) The high content of STIM1 in the PM is sufficient to activate SOCs; this is shown as a hypothetical interaction between STIM1 and SOCs. (E) In the “influence” model, the aggregated STIM1 in puncta near the PM conformationally couples to STIM1 preexisting in the PM and causes association and reorganization of STIM1 in the PM. (F) This reorganization induces formation of a similar hypothetical complex between STIM1 and SOCs, leading again to channel activation.