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

EMBO Molecular Medicine

Matthew G. Gold³  Steve L. Reichow⁴  Susan E. O'Neill⁴  Chad R. Weisbrod¹  Lorene K. Langeberg³  James E. Bruce¹  Tamir Gonen² 

[1] Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA;E-mail address: 关键词: AKAP;    AQP0;    cataract;    lens;    PKA;   

DOI  :  10.1002/emmm.201100184

来源: Wiley

【 摘 要 】

Abstract

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.

→See accompanying article http://dx.doi.org/10.1002/emmm.201100188

【 授权许可】

Unknown   
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