Organization and Ca2+ regulation of adenylyl cyclases in cAMP microdomains

Physiol Rev. 2007 Jul;87(3):965-1010. doi: 10.1152/physrev.00049.2006.


The adenylyl cyclases are variously regulated by G protein subunits, a number of serine/threonine and tyrosine protein kinases, and Ca(2+). In some physiological situations, this regulation can be readily incorporated into a hormonal cascade, controlling processes such as cardiac contractility or neurotransmitter release. However, the significance of some modes of regulation is obscure and is likely only to be apparent in explicit cellular contexts (or stages of the cell cycle). The regulation of many of the ACs by the ubiquitous second messenger Ca(2+) provides an overarching mechanism for integrating the activities of these two major signaling systems. Elaborate devices have been evolved to ensure that this interaction occurs, to guarantee the fidelity of the interaction, and to insulate the microenvironment in which it occurs. Subcellular targeting, as well as a variety of scaffolding devices, is used to promote interaction of the ACs with specific signaling proteins and regulatory factors to generate privileged domains for cAMP signaling. A direct consequence of this organization is that cAMP will exhibit distinct kinetics in discrete cellular domains. A variety of means are now available to study cAMP in these domains and to dissect their components in real time in live cells. These topics are explored within the present review.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Animals
  • Calcium Signaling / physiology*
  • Cyclic AMP / metabolism*
  • Protein Conformation
  • Protein Structure, Tertiary


  • Cyclic AMP
  • Adenylyl Cyclases