Calcium release‐activated calcium channels as signal transducers in T‐cells

Abstract

AbstractStimulation of T‐cell receptors by professional antigen presenting cells initiates several signaling cascades which finally lead to T‐cell activation and proliferation. One of the cascades induces a rise of the cytoplasmic IP3 concentration, which releases Ca2+ from the endoplasmic reticulum. This Ca2+ release alone, however, is not sufficient to activate Ca2+ dependent signal transduction and gene transcription in T‐cells. For T‐cell activation and proliferation, a sustained Ca2+ entry over the plasma membrane is needed. This Ca2+ entry is called storeoperated Ca2+ (SOC) entry, because it is activated by depletion of the Ca2+ stores. The first and best‐characterized member of the SOC channels is the Ca2+ release‐activated Ca2+ (CRAC) channel which is the predominant Ca2+ influx pathway in T‐cells. CRAC channels are highly selective for Ca2+ over all other cations and are responsible for the Ca2+ entry and subsequent sustained elevation of the intracellular Ca2+ concentration which is required for T‐cell activation. We discuss the role of CRAC channels for T‐cell activation and their potential to determine the quality and quantity of the T‐cell response.