Mechanisms of calcium signaling and function in lymphocytes

The multifunctional role for calcium during lymphocyte activation and differentiation is well established; yet how fate-specific changes in calcium concentration are produced, and how these signals are translated into distinct cellular responses, is not known. A critical role has been identified for store-operated calcium release-activated calcium (CRAG) channels; however, the lack of information concerning the structure and mechanism of store-dependent activation has limited our ability to define CRAC's role in the range of calcium-dependent responses of lymphocytes. Moreover, additional calcium-permeant cation channels have been recently identified in lymphocytes. These channels regulate functions distinct from those attributed to CRAG channels. Consequently, this review summarizes well-established mechanisms of calcium signaling and also considers recent findings which suggest that diverse and interacting pathways encode functionally specific calcium signals in lymphocytes. Speculation is also offered about how distinct patterns of calcium signaling are translated into diverse transcriptional responses.