New AMPA (glutamate) receptor interacting protein discovered

01 April 2010

Science Paper: New sensitive proteomics technologies of the CNCR research team of Ka Wan Li allowed the discovery of a novel protein interacting with AMPA receptors.

New sensitive proteomics technologies of the CNCR research team of Ka Wan Li allowed the discovery of a novel protein interacting with AMPA receptors. Together with collaborators from the University and Max Planck Institute of Heidelberg the protein was shown to affect postsynaptic physiology of the AMPA-type glutamate receptors. The findings are described in Science, March 19;327(5972):1518-22

Postsynaptic glutamate signalling crucially depends on the function of NMDA– and AMPA-type receptors (AMPARs). AMPARs play a crucial role in the plasticity of the postsynaptic element, for instance by stimulus-dependent cycling to and from the postsynaptic plasma membrane. In addition to the changing levels of AMPARs several interacting proteins of the AMPARs have been discovered over the last years. These proteins either play a role in the AMPAR localization to the postsynapse (e.g. TARP) or changing deactivation and desensitization kinetics (the recently discovered Cornichon protein). The newly discovered protein CKAMP44 is a single transmembrane protein, highly expressed in the hippocampal dentate gyrus, and acts at the AMPAR to modulate it’s decay time.

The protein was discovered by Volker Mack when performing his postdoc at the CNCR in the Li/ Smit team. The modulatory role of CKAMP44 was subsequently investigated by collaborators in Heidelberg and Tel Aviv.

Because AMPARs and their interactors are core to synaptic plasticity in hippocampus and cortex, the CNCR team expects that AMPAR interactors, among which CKAMP44, hold new promises for drug discovery aimed at therapeutic intervention of learning and memory processes.