CKAMP44: a brain-specific protein attenuating short-term synaptic plasticity in the dentate gyrus

Science. 2010 Mar 19;327(5972):1518-22. doi: 10.1126/science.1184178. Epub 2010 Feb 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / metabolism
  • Calcium Channels / metabolism
  • Dendritic Spines / metabolism
  • Dentate Gyrus / cytology
  • Dentate Gyrus / metabolism*
  • 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
  • Nerve Tissue Proteins / metabolism*
  • Neural Inhibition
  • Neuronal Plasticity*
  • Neurons / metabolism*
  • 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
  • Receptors, AMPA / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synapses / physiology*
  • Synaptic Transmission*
  • Xenopus laevis

Substances

  • CKAMP44 protein, mouse
  • Cacng2 protein, mouse
  • Calcium Channels
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Protein Isoforms
  • Receptors, AMPA
  • Recombinant Fusion Proteins
  • Glutamic Acid
  • Guanylate Kinases

Associated data

  • GENBANK/GU479981
  • GENBANK/GU479982