Papel de Orai, STIM y TRPC en la entrada de calcio

Abstract

In eukaryotic cells, ion calcium (Ca2+) is the most versatile signal involved in controlling cellular functions, since it participates in processes such as muscle contraction, reproduction and even cell death or apoptosis. Therefore, intracellular Ca2+ concentration ([Ca2+]c) is finely regulated, with mechanisms that increase or reduce [Ca2+]c. In this Thesis we have studied Ca2+ entry in platelets and HEK293, and especially the store-operated Ca2+ entry (SOCE), activated when the stores (mainly the endoplasmic reticulum) are emptied after Ca2+ release. Proteins such as STIM1 (sensor of the Ca2+ in the reticulum), Orai1 or TRPC channels participate in SOCE, and the function of the cellular cytoskeleton is very important, and so it is the support provided by lipid rafts, membrane domains rich in cholesterol. The results of this Thesis show that lipid rafts are important for the activation of SOCE, since disruption of these domains reduces the association between the proteins involved in this entry; but not for the maintenance of SOCE. Furthermore, the cytoskeleton participates in SOCE by regulating the interaction between the different proteins, and by supporting the association between calmodulin and the Ca2+ channels in the membrane. Also, the interaction between either calmodulin or IP3Rs with the CIRB domain of TRPC6 regulates both the thrombin-stimulated Ca2+ entry and the aggregation of platelets.