PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons
E-Collection

Related Articles
Families in Gene Neighborhoods
June 2015
Signaling: A Platform for Opposing Functions
May 2015
Nuclear Pore Complex: A Flexible Transporter
February 2015
Nuclear Pore Complex: Higher Resolution of Macromolecules
February 2015
Nuclear Pore Complex: Integrative Approach to Probe Nup133
February 2015
Piecing Together the Nuclear Pore Complex
February 2015
iTRAQing the Ubiquitinome
July 2014
CAAX Endoproteases
August 2013
The Immune System: A Strong Competitor
June 2013
The Immune System: Strand Swapping for T-Cell Inhibition
June 2013
PDZ Domains
April 2013
Protein Interaction Networks: Adding Structure to Protein Networks
April 2013
Protein Interaction Networks: Morph to Assemble
April 2013
Protein Interaction Networks: Reading Between the Lines
April 2013
Protein Interaction Networks: When the Sum Is Greater than the Parts
April 2013
Alpha-Catenin Connections
March 2013
Cytochrome Oxidase
November 2012
Bacterial Phosphotransferase System
October 2012
Solute Channels
September 2012
Budding ensemble
August 2012
The machines behind the spindle assembly checkpoint
June 2012
G Protein-Coupled Receptors
May 2012
Revealing the Nuclear Pore Complex
March 2012
Topping off the proteasome
March 2012
Anchoring's the way
February 2012
Reading out regioselectivity
December 2011
An effective and cooperative dimer
November 2011
PDZ domains: sometimes it takes two
November 2011
Raising a glass to GLIC
August 2011
A2A Adenosine Receptor
May 2011
A growing family
February 2011
FERM-ly bound
February 2011
CXCR4
January 2011
Guard cells pick up the SLAC
December 2010
Zinc Transporter ZntB
July 2010
Zinc Transporter ZntB
July 2010
Importance of extension for integrin
June 2010
Spot protein-protein interactions… fast
March 2010
Alg13 Subunit of N-Acetylglucosamine Transferase
February 2010
Urea transporter
February 2010
Two-component signaling
December 2009
ABA receptor...this time for real?
November 2009
Network coverage
November 2009
Get3 into the groove
October 2009
Guanine Nucleotide Exchange Factor Vav1 and Rho GTPase Rac1
October 2009
GPCR subunits: Separate but not equal
September 2009
Proofreading RNA
July 2009
Ribonuclease and Ribonuclease Inhibitor
April 2009
The elusive helicase
April 2009
Click for cancer-protein interactions
December 2008

Research Themes Protein-protein interactions

Anchoring's the way

SBKB [doi:10.1038/sbkb.2011.62]
Featured Article - February 2012
Short description: New insights into the regulation of AQP0 reveal mechanisms involved in cataract development.

The C-terminal domain of AQP0 has an AKAP2 binding site (green) and a helical segment (yellow) where PKA-mediated phosphorylation occurs. (PDB: 2B6P) figure courtesy of Tamir Gonen.

While most tissues receive nutrients via blood vessels, the ocular lens, which must be transparent to properly focus light, lacks a conventional vascular system. Instead, the lens has an internal circulation system based on membrane channel and transporter proteins. These proteins maintain lens transparency by enabling a constant flow of water, ions, second messengers, and metabolites. Cataract, a clouding of the ocular lens, is the leading cause of blindness worldwide.

Aquaporins are transmembrane proteins that regulate the flow of water across biological membranes. One of the primary proteins involved in maintaining the flow of water throughout the lens is the water channel aquaporin-0 (AQP0). The opening and closing of AQP0 are regulated by several mechanisms. For example, binding of Ca2+/calmodulin closes the pore, whereas phosphorylation of AQP0 in the calmodulin-binding region opens the channel. However, the details involved in this process had not been previously identified.

Now, Gold and colleagues (PSI TEMIMPS), have identified the players involved in opening AQP0 by phosphorylation. The authors noted that the sequence surrounding the phosphorylation site in AQP0 corresponds to a protein kinase A (PKA) recognition motif. Because PKA is often brought into contact with its substrates by A-kinase anchoring proteins (AKAPs), the authors proceeded to identify potential AKAPs in the lens. Immunoblotting of lens homogenates and fixed lenses revealed that AKAP2 interacts with PKA and localizes to the lens cortex. AQP0 was also found to associate with AKAP2 via the channel's cytoplasmic tail. The authors verified by mass spectrometry that PKA could phosphorylate Ser235 in AQP0. Ser235 is located in the calmodulin-binding domain of AQP0, and phosphorylation at this site prevents binding between AQP0 and calmodulin. Therefore, the authors developed a model by which AKAP2 brings PKA and AQP0 into close proximity, enabling phosphorylation and subsequent activation of AQP0 by PKA and regulating water permeability in the lens.

To verify the relevance of their findings, the authors disrupted the interaction between PKA and AQP0 in the lens in vivo. Displacement of PKA led to cataract development in the lens and increased lens opacity. This work represents the first direct demonstration of the function of AKAP2 and elucidates one of the mechanisms that lead to cataract development.

Jennifer Cable

References

  1. M.G. Gold et al. AKAP2 anchors PKA with aquaporin-0 to support ocular lens transparency.
    EMBO Mol Med. 4, 1-12 (2011). doi:10.1002/emmm.201100184

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health