SOCIC: the store-operated calcium influx complex.

Depletion of intracellular calcium stores via activation of G-protein-coupled receptors associated to the inositol trisphosphate cascade, or by the blockade of the endoplasmic reticulum calcium APTase (SERCA) results in the activation of calcium influx via the so-called store-operated channels (SOCs). The recent identification of STIM1 as the putative sensing molecule responsible for communicating the depleted state of intracellular calcium stores to the plasma membrane channel highlights the relevance of protein complexes in calcium signaling. Further developments in this area identify Orai as part of the store-operated channel complex. Upon depletion of intracellular calcium stores, STIM1 (at the ER) and Orai (at the plasma membrane) aggregate into macromolecular complexes. This molecular aggregation appears to be necessary to induce activation of calcium influx. Several studies have identified novel members from what I would like to define here as the store-operated calcium influx complex (SOCIC), such as the TRPC1 channel, SERCA and the microtubule end tracking protein, EB1. An orchestrated series of events involving the association and dissociation of several protein complexes culminate with the activation of calcium influx upon depletion of the ER. There are other likely players in this sophisticated signaling mechanism, waiting to be uncovered. The SOCIC assembly does not appear to occur in random areas of the plasma membrane, but rather in highly specialized areas known as lipid raft domains. These results strongly suggest that not only proteins but lipids also may be part or active players in the modulation of the store-operated calcium entry (SOCE). In this review we will analyze the evidence supporting macromolecular complex assembly as a prerequisite for SOC activation. We will highlight the evidence showing novel members from SOCIC and speculate about possible yet undiscovered members and players in this highly regulated calcium signaling mechanism. Finally we will discuss about the role of lipid raft domains in controlling store- and agonist-activated calcium influx. 2010 Elsevier Ltd. All rights reserved.