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Science ; 327(5972): 1518-22, 2010 Mar 19.
Article in English | MEDLINE | ID: mdl-20185686

ABSTRACT

CKAMP44, identified here by a proteomic approach, is a brain-specific type I transmembrane protein that associates with AMPA receptors in synaptic spines. CKAMP44 expressed in Xenopus oocytes reduced GluA1- and A2-mediated steady-state currents, but did not affect kainate- or N-methyl-D-aspartate (NMDA) receptor-mediated currents. Mouse hippocampal CA1 pyramidal neurons expressed CKAMP44 at low abundance, and overexpression of CKAMP44 led to stronger and faster AMPA receptor desensitization, slower recovery from desensitization, and a reduction in the paired-pulse ratio of AMPA currents. By contrast, dentate gyrus granule cells exhibited strong CKAMP44 expression, and CKAMP44 knockout increased the paired-pulse ratio of AMPA currents in lateral and medial perforant path-granule cell synapses. CKAMP44 thus modulates short-term plasticity at specific excitatory synapses.


Subject(s)
Dentate Gyrus/metabolism , Nerve Tissue Proteins/metabolism , Neuronal Plasticity , Neurons/metabolism , Receptors, AMPA/metabolism , Synapses/physiology , Synaptic Transmission , Animals , CA1 Region, Hippocampal/metabolism , Calcium Channels/metabolism , Dendritic Spines/metabolism , Dentate Gyrus/cytology , Disks Large Homolog 4 Protein , Excitatory Postsynaptic Potentials , Glutamic Acid/metabolism , Guanylate Kinases , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/metabolism , Mice , Mice, Knockout , Miniature Postsynaptic Potentials , Molecular Sequence Data , Nerve Tissue Proteins/chemistry , Nerve Tissue Proteins/genetics , Neural Inhibition , Oocytes/metabolism , Patch-Clamp Techniques , Perforant Pathway , Protein Interaction Domains and Motifs , Protein Isoforms/genetics , Protein Isoforms/metabolism , Proteomics , Pyramidal Cells/metabolism , Receptors, AMPA/chemistry , Recombinant Fusion Proteins/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Xenopus laevis
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