1. CKAMP44: a brain-specific protein attenuating short-term synaptic plasticity in the dentate gyrus.
- Author
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von Engelhardt J, Mack V, Sprengel R, Kavenstock N, Li KW, Stern-Bach Y, Smit AB, Seeburg PH, and Monyer H
- Subjects
- 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, Dentate Gyrus metabolism, Nerve Tissue Proteins metabolism, Neuronal Plasticity, Neurons metabolism, Receptors, AMPA metabolism, Synapses physiology, Synaptic Transmission
- 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.
- Published
- 2010
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