FUNCTION FOLLOWS FORM - THE ROLE OF STORE-OPERATED CALCIUM CHANNELS IN T-CELL ACTIVATION

In T lymphocytes and most other nonexcitable cells, store-operated cha nnels (SOCs) are activated through an unknown mechanism following depl etion of intracellular Ca2+ stores, Several lines of evidence indicate that a specific SOC, known as the Ca2+ release-activated Ca2+ (CRAC) channel, mediates the influx of Ca2+ that occurs in response to stimul ation through the T-cell receptor, CRAC channels are characterized by an extremely high Ca2+ selectivity and low unitary conductance and by a sensitivity to positive and negative regulation by calcium, Stimulat ion of T cells elicits a variety of Ca2+ patterns, including spikes, o scillations, and maintained plateaus, The mechanisms underlying these responses may involve delayed feedback between Ca2+ stores, [Ca2+](i) and CRAC channels as well as the uptake and release of Ca2+ by mitocho ndria. Information may be encoded in the amplitude and duration of Ca2 + signals, as the spike and plateau Ca2+ response differentially activ ate transcriptional pathways in B cells, CRAC-deficient T-cell mutants and mammalian homologs of the Drosophila trp protein present attracti ve opportunities for elucidating the molecular basis and consequences of store-operated calcium influx in T cells.