mGluR1/5-Dependent Long-Term Depression Requires the Regulated Ectodomain Cleavage of Neuronal Pentraxin NPR by TACE

Richard W. Cho, Joo Min Park, Steffen B.E. Wolff, Desheng Xu, Carsten Hopf, Jin ah Kim, Radhika C. Reddy, Ronald S. Petralia, Mark S. Perin, David J. Linden, Paul F. Worley

Research output: Contribution to journalArticle

Abstract

Matrix metalloproteases (MMPs) play a role in remodeling the extracellular matrix during brain development and have been implicated in synaptic plasticity. Here, we report that a member of the neuronal pentraxin (NP) family, neuronal pentraxin receptor (NPR), undergoes regulated cleavage by the MMP tumor necrosis factor-α converting enzyme (TACE). NPR is enriched at excitatory synapses where it associates with AMPA-type glutamate receptors (AMPAR) and enhances synaptogenesis. However, in response to activation of group 1 mGluRs (mGluR1/5), TACE cleaves NPR and releases the pentraxin domain from its N-terminal transmembrane domain. Cleaved NPR rapidly accumulates in endosomes where it colocalizes with AMPAR. This process is necessary for mGluR1/5-dependent LTD in hippocampal and cerebellar synapses. These observations suggest that cleaved NPR functions to "capture" AMPAR for endocytosis and reveal a bifunctional role of NPs in both synapse strengthening and weakening.

Original languageEnglish (US)
Pages (from-to)858-871
Number of pages14
JournalNeuron
Volume57
Issue number6
DOIs
StatePublished - Mar 27 2008

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Keywords

  • CELLBIO
  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cho, R. W., Park, J. M., Wolff, S. B. E., Xu, D., Hopf, C., Kim, J. A., Reddy, R. C., Petralia, R. S., Perin, M. S., Linden, D. J., & Worley, P. F. (2008). mGluR1/5-Dependent Long-Term Depression Requires the Regulated Ectodomain Cleavage of Neuronal Pentraxin NPR by TACE. Neuron, 57(6), 858-871. https://doi.org/10.1016/j.neuron.2008.01.010