Function Follows Form: The Role of Store-Operated Calcium Channels in T-Cell Activation

Abstract

In T lymphocytes and most other nonexcitable cells, store-operated channels (SOCs) are activated through an unknown mechanism following depletion 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 stimulation 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. Stimulation of T cells elicits a variety of Ca²⁺ patterns, including spikes, oscillations, 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 mitochondria. Information may be encoded in the amplitude and duration of Ca²⁺ signals, as the spike and plateau Ca²⁺ response differentially activate transcriptional pathways in B cells. CRAC-deficient T-cell mutants and mammalian homologs of the <i>Drosophila trp </i>protein present attractive opportunities for elucidating the molecular basis and consequences of store-operated calcium influx in T cells.