New aspects of the contribution of ER to SOCE regulation the contribution of SERCA to the regulation of SOCE

Abstract

Apart from amplifying the cytosolic Ca2+ signals generated by Ca2+ mobilization from the endoplasmic reticulum (ER), capacitative calcium entry (CCE) is essential for quick refilling of the ER, which is necessary for repeating Ca2+ signals. SERCA is the third element of CCE. It co-localizes with STIM1 and Orai1 at puncta where it is tightly coupled to plasma membrane store-operated Ca2+ channels (SOC). This allows an extremely efficient refilling of the ER stores with the Ca2+ entering through activated SOC. Whereas ER takes up most of the store-operated Ca2+ entry, mitochondria takes up a very little part. Low mitochondrial Ca2+ uptake can be explained by longer distance to SOC and lower Ca2+ affinity of mitochondrial uptake mechanisms.