Spatial organization of intracellular Ca2+ signals

Semin Cell Dev Biol. 2012 Apr;23(2):172-80. doi: 10.1016/j.semcdb.2011.09.006. Epub 2011 Sep 13.


The ability of Ca(2+), the simplest of all intracellular messengers, selectively to regulate so many cellular behaviours is due largely to the complex spatiotemporal organization of intracellular Ca(2+) signals. Most signalling pathways, including those that culminate in Ca(2+) signals, comprise sequences of protein-protein interactions linked by diffusible messengers. Using specific examples to illustrate key principles, we consider the roles of both components in defining the spatial organization of Ca(2+) signals. We discuss evidence that regulation of most Ca(2+) channels by Ca(2+) contributes to controlling the duration of Ca(2+) signals, to signal integration and, via Ca(2+)-induced Ca(2+) release, to defining the spatial spread of Ca(2+) signals. We distinguish two types of protein-protein interaction: scaffolds that allow rapid local transfer of diffusible messengers between signalling proteins, and interactions that directly transfer information between signalling proteins. Store-operated Ca(2+) entry provides a ubiquitous example of the latter, and it serves also to illustrate how Ca(2+) signals can be organized at different levels of spatial organization - from interactions between proteins to interactions between organelles.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Calcium Signaling*
  • Cell Communication
  • Cytosol / metabolism
  • Diffusion
  • Humans
  • Lysosomes / metabolism
  • NADP / analogs & derivatives
  • NADP / metabolism
  • Protein Binding
  • Protein Interaction Maps
  • Protein Transport


  • Calcium Channels
  • NADP
  • Calcium