Physiological roles for G protein-regulated adenylyl cyclase isoforms: insights from knockout and overexpression studies

Neurosignals. 2009;17(1):5-22. doi: 10.1159/000166277. Epub 2008 Oct 24.


Cyclic AMP is a universal second messenger, produced by a family of adenylyl cyclase (AC) enzymes. The last three decades have brought a wealth of new information about the regulation of cyclic AMP production by ACs. Nine hormone-sensitive, membrane-bound AC isoforms have been identified in addition to a tenth isoform that lacks membrane spans and more closely resembles the cyanobacterial AC enzymes. New model systems for purifying and characterizing the catalytic domains of AC have led to the crystal structure of these domains and the mapping of numerous interaction sites. However, big hurdles remain in unraveling the roles of individual AC isoforms and their regulation in physiological systems. In this review we explore the latest on AC knockout and overexpression studies to better understand the roles of G protein regulation of ACs in the brain, olfactory bulb, and heart.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adenylyl Cyclases / chemistry
  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / metabolism*
  • Animals
  • Apoptosis / physiology
  • Brain / metabolism
  • Calcium / metabolism
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Isoenzymes / chemistry
  • Isoenzymes / metabolism
  • Memory / physiology
  • Myocardium / metabolism
  • Nerve Degeneration / physiopathology
  • Neuronal Plasticity / physiology
  • Olfactory Bulb / metabolism
  • Pain / physiopathology
  • Protein Conformation
  • Substance-Related Disorders / physiopathology


  • Isoenzymes
  • Heterotrimeric GTP-Binding Proteins
  • Adenylyl Cyclases
  • Calcium