CKAMP44: A Brain-Specific Protein Attenuating Short-Term Synaptic Plasticity in the Dentate Gyrus

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Science  25 Feb 2010:
DOI: 10.1126/science.1184178


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 reduces GluA1- and A2-mediated steady-state currents, but fails to affect kainate- or NMDA receptor-mediated currents. Mouse hippocampal CA1 pyramidal neurons express CKAMP44 at low levels, and overexpression of CKAMP44 leads to stronger and faster AMPA receptor desensitization, slower recovery from desensitization, and a reduction in the paired-pulse ratio of AMPA currents. In contrast, dentate gyrus granule cells exhibit strong CKAMP44 expression, and here, CKAMP44 knockout increases 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.