The multiple and enigmatic roles of guanylyl cyclase C in intestinal homeostasis

FEBS Lett. 2012 Aug 31;586(18):2835-40. doi: 10.1016/j.febslet.2012.07.028. Epub 2012 Jul 20.


Guanylyl cyclase C (GC-C) is predominantly expressed in intestinal epithelial cells and serves as the receptor for the gastrointestinal hormones guanylin and uroguanylin, and the heat-stable enterotoxin, the causative agent for Travellers' Diarrhea. Activation of GC-C results in an increase in intracellular levels of cGMP, which can regulate fluid and ion secretion, colon cell proliferation, and the gut immune system. This review highlights recent findings arising from studies in the GC-C knock-out mouse, along with enigmatic results obtained from the first descriptions of human disease caused by mutations in the GC-C gene. We provide some insight into these new findings and comment on areas of future study, which may enhance our knowledge of this evolutionarily conserved receptor and signaling system.

Publication types

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

MeSH terms

  • Animals
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Cyclic GMP / metabolism
  • Enzyme Activation
  • Feeding Behavior
  • Homeostasis*
  • Humans
  • Intestines / enzymology
  • Intestines / physiology*
  • Mice
  • Receptors, Enterotoxin
  • Receptors, Guanylate Cyclase-Coupled / metabolism*
  • Receptors, Peptide / metabolism*


  • Receptors, Peptide
  • Receptors, Enterotoxin
  • Receptors, Guanylate Cyclase-Coupled
  • Cyclic GMP