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Jakob von EngelhardtCKAMP44 : A novel modulator of AMPA receptor-mediated currents

Abstract :


AMPA receptors mediate most of the fast excitatory transmission in the central nervous system.
Their function is modulated by the interaction with different auxiliary proteins such as TARPS (transmembrane AMPA receptor regulatory proteins) or cornichons. Recently, we identified a new AMPA receptor interacting protein (CKAMP44 = Cystine-knot AMPA receptor modulating protein) using immunoprecipitation and mass spectrometry of AMPA receptor complexes. This brain specific type I transmembrane protein of 424 amino acids contains a cysteine rich extracellular region, a single putative transmembrane segment and an intracellular region with a PDZ type II ligand motif at its C-terminus. The extracellular cysteines might form a Cystine-knot structure. Western blot analyses and immunocytochemical experiments indicated that CKAMP44 is synaptically localized. Electrophysiological experiments using Xenopus laevis oocytes and acute brain slices of control, CKAMP44 knockout and CKAMP44 overexpressing mice revealed that CKAMP44 modulates AMPA receptor function by increasing deactivation time constant, decreasing desensitization time constant, slowing recovery from desensitization and increasing glutamate affinity. By its influence on desensitization, CKAMP44 changes short-term plasticity of synaptic AMPA receptor-mediated currents in the dentate gyrus. 

Selected publications

von Engelhardt J, Mack V, Sprengel R, Kavenstock N, Li KW, Stern-Bach Y, Smit AB, Seeburg PH, Monyer H (2010) CKAMP44: A Brain Specific Protein Attenuating Short-term Synaptic Plasticity in Dentate Gyrus Science 327:1518-1522

Daniel Choquet