thapsigargin and Severe-Combined-Immunodeficiency

Store-operated calcium entry (SOCE) is a major mechanism for Ca(2+) entry in excitable and non-excitable cells. The best-characterised store-operated current is I(CRAC), but other currents activated by Ca(2+) store depletion have also been reported. The recent identification of the proteins stromal interaction molecule 1 (STIM1) and Orai1 has shed new light on the nature and regulation of SOC channels. STIM1 has been presented as the endoplasmic reticulum (ER) Ca(2+) sensor that communicates the content of the Ca(2+) stores to the store-operated channels, a mechanism that involves redistribution of STIM1 to peripheral ER sites and co-clustering with the Ca(2+) channel subunit, Orai1. Interestingly, TRPC1, which has long been proposed as a SOC channel candidate, associates with Orai1 and STIM1 in a ternary complex that appears to increase the variability of SOC currents available to modulate cell function.

Topics: Animals; Calcium; Calcium Channels; Calcium Signaling; Cations; Cell Adhesion Molecules; Drosophila Proteins; Humans; Ion Transport; Membrane Proteins; Multiprotein Complexes; Neoplasm Proteins; ORAI1 Protein; ORAI2 Protein; Protein Interaction Mapping; Protein Multimerization; Severe Combined Immunodeficiency; Stromal Interaction Molecule 1; Stromal Interaction Molecule 2; Thapsigargin; TRPC Cation Channels