Signaling through Ca2+ Microdomains from Store-Operated CRAC Channels

Abstract

Calcium (Ca²⁺) ion microdomains are subcellular regions of high Ca²⁺ concentration that develop rapidly near open Ca²⁺ channels in the plasma membrane or internal stores and generate local regions of high Ca²⁺ concentration. These microdomains are remarkably versatile in that they activate a range of responses that differ enormously in both their temporal and spatial profile. In this review, we describe how Ca²⁺ microdomains generated by store-operated calcium channels, a widespread and conserved Ca²⁺ entry pathway, stimulate different signaling pathways, and how the spatial extent of a Ca²⁺ microdomain can be influenced by Ca²⁺ ATPase pumps.

Figure 1.

Cartoon summarizes various responses activated by local calcium (Ca²⁺) entry through Ca²⁺ release-activated Ca²⁺ (CRAC) channels. PMCA, Plasma membrane Ca²⁺ ATPase; ER, endoplasmic reticulum; LTC₄, leukotriene C₄; NFAT, nuclear factor of activated T cells.

Figure 2.

The cartoon summarizes two models (A,B) for how the plasma membrane Ca²⁺ ATPase (PMCA) pump activity is regulated at the immunological synapse in T cells (see text for further details). CRAC, Ca²⁺ release-activated Ca²⁺; ER, endoplasmic reticulum.