[Immunodeficiencies and pathologies associated with mutations in STIM/ORAI, a membrane complex in the heart of calcium signalling]. / Immunodéficiences et pathologies associées aux mutations dans STIM/ORAI - Un complexe membranaire au cœur de la signalisation calcique.

ABSTRACT

Six years ago, STIM1 (stromal interaction molecule 1) was identified as an essential component of store-operated calcium channels and in less than one year teamed up with its first partner ORAI1 in immune cells to reconstitute CRAC (calcium-release activated current) channel function. Since then, STIM1 and ORAI1 have developed an ever increasing social network and to date are now linked to nine families of proteins involved in calcium signalling. As a result of this, STIM1 and ORAI1 are now involved in three separate calcium entry pathways, Icrac, Iarc (arachidonic regulated calcium current) and voltage-dependent channels. Physiopathological roles of STIM1 and ORAI1 were first described in the immunological system but, as main actors at the central node in the calcium signalling network, there are now clear evidences that mutations in genes coding STIM1 or ORAI1 interfere with several other diseases.