Store-operated Ca²⁺-entry and adenylyl cyclase.

One of the longest-standing effects of SOCE is in its selective regulation of Ca(2+)-sensitive adenylyl cyclase (AC) activity in non-excitable cells. Remarkably it was this source of Ca(2+) (SOCE) rather than the apparent magnitude of the Ca(2+)-rise that conferred AC responsiveness. The molecular basis for this dependence is now resolved in the case of adenylyl cyclase 8 (AC8). Sensors for Ca(2+) and cAMP targeted to ACs have been particularly useful in dissecting the influences upon and composition of what turn out to be signalling microdomains centred on ACs. A number of physiological processes depend on the regulation by SOCE of ACs, but the issue is under-studied. Here I will expand on these topics and point to some immediate unresolved questions.