CRAC channels and Ca2+ signaling in mast cells

Mast cells are integral members of the immune system. Upon activation by a rise in cytoplasmic Ca2+, they release a battery of paracrine signals, chemokines, and cytokines, which help sculpt the subsequent immune response. Ca2+ entry through store-operated Ca2+ release-activated Ca2+ (CRAC) channels in the plasma membrane is central for driving most of these responses. The molecular basis of the CRAC channel has been identified, with Orai1 forming the channel pore. Recent work has revealed that a range of mast cell responses are activated by spatially restricted Ca2+ signals just below the plasma membrane. These Ca2+ microdomains can activate cytosolic enzymes, leading to the generation of intracellular messengers as well as proinflammatory molecules like LTC4. In this review, we describe key features of CRAC channels in mast cells, how they generate local Ca2+ signals, and how the cell can decode these restricted signals to generate a raft of responses.