CIF and other mysteries of the store-operated Ca2+-entry pathway

Trends Biochem Sci. 2005 Jul;30(7):378-87. doi: 10.1016/j.tibs.2005.05.009.


The molecular mechanism of the store-operated Ca2+-entry (SOCE) pathway remains one of the most intriguing and long lasting mysteries of Ca2+ signaling. The elusive calcium influx factor (CIF) that is produced upon depletion of Ca2+ stores has attracted growing attention, triggered by new discoveries that filled the gap in the chain of reactions leading to activation of store-operated channels and Ca2+ entry. Ca2+-independent phospholipase A2 emerged as a target of CIF, and a major determinant of the SOCE mechanism. Here, we present our viewpoint on CIF and conformational-coupling models of SOCE from a historical perspective, trying to resolve some of the problem areas, and summarizing our present knowledge on how depletion of intracellular Ca2+ stores signals to plasma membrane channels to open and provide Ca2+ influx that is required for many important physiological functions.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Factors / metabolism*
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Calcium Signaling / physiology*
  • Humans
  • Models, Biological


  • Biological Factors
  • Calcium Channels
  • Calcium