Anchoring of aquaporin-4 in brain: molecular mechanisms and implications for the physiology and pathophysiology of water transport

Neuroscience. 2004;129(4):999-1010. doi: 10.1016/j.neuroscience.2004.08.049.


Astrocytes show an enrichment of aquaporin-4 (AQP4) in those parts of the plasma membrane that are apposed to pial or perivascular basal laminae. This observation begged the following questions: 1, What are the molecular mechanisms that are responsible for the site specific anchoring of AQP4? 2, What are the physiological and pathophysiological roles of the AQP4 pools at these specialized membrane domains? Recent studies suggest that the site specific anchoring depends on the dystrophin complex. Further, alpha-syntrophin (a member of the dystrophin complex) is required to maintain a polarized expression of AQP4 in the perivascular membranes. Hence transgenic mice deficient in alpha-syntrophin provided a model where the perivascular pool of AQP4 could be removed for assessment of its functional roles. Data suggest that the perivascular pool of AQP4 plays a role in edema formation and that this pool (through its serial coupling with the AQP4 pools in other astrocyte membranes) is involved in K(+) siphoning. In the cerebral cortex, the astrocyte membrane domain contacting the pial basal lamina differs from the perivascular membrane domain in regard to the mechanisms for AQP anchoring. Thus deletion of alpha-syntrophin causes only a 50% loss of AQP4 from the former membrane (compared with a 90% loss in the latter), pointing to the existence of additional anchoring proteins. We will also discuss the subcellular distribution and anchoring of AQP4 in the other cell types that express this protein: endothelial cells, ependymal cells, and the specialized astrocytes of the osmosensitive organs.

Publication types

  • Review

MeSH terms

  • Animals
  • Aquaporin 4
  • Aquaporins / metabolism
  • Aquaporins / physiology*
  • Astrocytes / physiology
  • Astrocytes / ultrastructure
  • Biological Transport / physiology
  • Blood-Brain Barrier / physiology*
  • Blood-Brain Barrier / physiopathology
  • Blood-Brain Barrier / ultrastructure
  • Brain / physiology*
  • Brain / physiopathology
  • Brain / ultrastructure
  • Brain Edema / physiopathology
  • Calcium-Binding Proteins
  • Cell Membrane / physiology
  • Cell Membrane / ultrastructure
  • Membrane Proteins / genetics
  • Mice
  • Muscle Proteins / genetics
  • Water / metabolism*
  • Water-Electrolyte Balance / physiology*


  • Aqp4 protein, mouse
  • Aquaporin 4
  • Aquaporins
  • Calcium-Binding Proteins
  • Membrane Proteins
  • Muscle Proteins
  • syntrophin alpha1
  • Water