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

Abstract

Stimulation 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.