AKAP2 anchors PKA with aquaporin-0 to support ocular lens transparency

EMBO Mol Med. 2012 Jan;4(1):15-26. doi: 10.1002/emmm.201100184. Epub 2011 Nov 16.


A decline in ocular lens transparency known as cataract afflicts 90% of individuals by the age 70. Chronic deterioration of lens tissue occurs as a pathophysiological consequence of defective water and nutrient circulation through channel and transporter proteins. A key component is the aquaporin-0 (AQP0) water channel whose permeability is tightly regulated in healthy lenses. Using a variety of cellular and biochemical approaches we have discovered that products of the A-kinase anchoring protein 2 gene (AKAP2/AKAP-KL) form a stable complex with AQP0 to sequester protein kinase A (PKA) with the channel. This permits PKA phosphorylation of serine 235 within a calmodulin (CaM)-binding domain of AQP0. The additional negative charge introduced by phosphoserine 235 perturbs electrostatic interactions between AQP0 and CaM to favour water influx through the channel. In isolated mouse lenses, displacement of PKA from the AKAP2-AQP0 channel complex promotes cortical cataracts as characterized by severe opacities and cellular damage. Thus, anchored PKA modulation of AQP0 is a homeostatic mechanism that must be physically intact to preserve lens transparency.

Publication types

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

MeSH terms

  • A Kinase Anchor Proteins / metabolism*
  • Animals
  • Aquaporins / chemistry
  • Aquaporins / metabolism*
  • Calmodulin / metabolism
  • Cataract / metabolism
  • Cataract / pathology
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Eye Proteins / chemistry
  • Eye Proteins / metabolism*
  • Lens, Crystalline / enzymology
  • Lens, Crystalline / metabolism*
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Phosphopeptides / analysis
  • Phosphorylation
  • Protein Binding
  • Sheep
  • Static Electricity
  • Water / metabolism


  • A Kinase Anchor Proteins
  • Aquaporins
  • Calmodulin
  • Eye Proteins
  • Membrane Proteins
  • Pakap protein, mouse
  • Phosphopeptides
  • aquaporin 0
  • Water
  • Cyclic AMP-Dependent Protein Kinases