Weft Warp and Weave: The Intricate Tapestry of Calcium Channels Regulating T Lymphocyte Function

摘要

Calcium (Ca²⁺) is a universal second messenger important for T lymphocyte homeostasis, activation, proliferation, differentiation, and apoptosis. The events surrounding Ca²⁺ mobilization in lymphocytes are tightly regulated and involve the coordination of diverse ion channels, membrane receptors, and signaling molecules. A mechanism termed store-operated Ca²⁺ entry (SOCE), causes depletion of endoplasmic reticulum (ER) Ca²⁺ stores following T cell receptor (TCR) engagement and triggers a sustained influx of extracellular Ca²⁺ through Ca²⁺ release-activated Ca²⁺ (CRAC) channels in the plasma membrane. The ER Ca²⁺ sensing molecule, stromal interaction molecule 1 (STIM1), and a pore-forming plasma membrane protein, ORAI1, have been identified as important mediators of SOCE. Here, we review the role of several additional families of Ca²⁺ channels expressed on the plasma membrane of T cells that likely contribute to Ca²⁺ influx following TCR engagement, particularly highlighting an important role for voltage-dependent Ca²⁺ channels (CaV) in T lymphocyte biology.