Mid-range Ca2+ signalling mediated by functional coupling between store-operated Ca2+ entry and IP3-dependent Ca2+ release

This is the authors' abstract. We don't add key points for this paper.

The versatility and universality of Ca2+ signals stem from the breadth of their spatial and temporal dynamics. Spatially, Ca2+ signalling is well studied in the microdomain scale, close to a Ca2+ channel, and at the whole-cell level. However, little is known about how local Ca2+ signals are regulated to specifically activate spatially distant effectors without a global Ca2+ rise. Here we show that an intricate coupling between the inositol 1,4,5 trisphosphate (IP3) receptor, SERCA pump and store-operated Ca2+ entry (SOCE) allows for efficient mid-range Ca2+ signalling. Ca2+ flowing through SOCE is taken up into the ER lumen by the SERCA pump, only to be re-released by IP3Rs to activate distal Ca2+-activated Cl− channels (CaCCs). This CaCC regulation contributes to setting the membrane potential of the cell. Hence functional coupling between SOCE, SERCA and IP3R limits local Ca2+ diffusion and funnels Ca2+ through the ER lumen to activate a spatially separate Ca2+ effector. It remains unclear how localized calcium influx activates distant effectors in the absence of a global Ca2+ rise. Courjaret and Machaca find that mid-range Ca2+ signalling is mediated by coupling between localized store-operated calcium entry and distal IP3-dependent Ca2+ release to activate Cl−channels.