Role of STIM and Orai proteins in the store-operated calcium signaling pathway

Thamara Hewavitharana, Xiaoxiang Deng, Jonathan Soboloff, Donald L. Gill

Research output: Contribution to journalArticlepeer-review

154 Scopus citations


Ca2+ signals are universal among cells in regulating a spectrum of cellular responses. Phospholipase C-coupled receptors activate two components of Ca2+ signals-rapid Ca2+ release from ER stores, followed by slower Ca2+ entry from outside the cell. The coupling process between ER and PM to mediate this "store-operated" Ca2+ entry process remained until recently a molecular mystery. The recent discovery of the necessity for STIM1 and Orai proteins in this process has provided crucial information on the coupling mechanism between stores and PM Ca2+ entry. STIM1 is a single spanning membrane protein with an unpaired Ca2+ binding EF-hand and appears to function as the sensor of ER luminal Ca2+, and, through redistribution in the ER, transduces information directly to the PM. Orai1 is a tetra-spanning PM protein and functions as the highly Ca2+-selective channel in the PM that is gated through interactions with the store-activated ER Ca2+ sensor. Recent evidence shows the two proteins together are necessary and sufficient for the function of store-operated Ca2+ entry. However, many questions arise about how and where the interactions of the STIM1 and Orai1 proteins occur within cells. Here we discuss recent information and ideas about the coupling between these proteins that leads to store-operated channel activation.

Original languageEnglish (US)
Pages (from-to)173-182
Number of pages10
JournalCell Calcium
Issue number2
StatePublished - Aug 2007

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology


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