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Science 327 (5972): 1518-1522

Copyright © 2010 by the American Association for the Advancement of Science

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

Jakob von Engelhardt,1,* Volker Mack,1,2,* Rolf Sprengel,3 Netta Kavenstock,4 Ka Wan Li,2 Yael Stern-Bach,4 August B. Smit,2 Peter H. Seeburg,3 Hannah Monyer1,{dagger}

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.

1 Department of Clinical Neurobiology, University of Heidelberg, 6910 Heidelberg, Germany.
2 Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit, 1081 HV Amsterdam, the Netherlands.
3 Department of Molecular Neurobiology, Max Planck Institute for Medical Research, 69120 Heidelberg, Germany.
4 Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada (IMRIC), the Hebrew University–Hadassah Medical School, Jerusalem 91120, Israel.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: monyer{at}

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