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

Fingerprint

AMPA Receptors
Glutamate Receptors
Synapses
Metalloproteases
Neuronal Plasticity
Endosomes
Endocytosis
Extracellular Matrix
Tumor Necrosis Factor-alpha
metabotropic glutamate receptor type 1
neuronal pentraxin receptor
neuronal pentraxin
Brain

Keywords

  • CELLBIO
  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

mGluR1/5-Dependent Long-Term Depression Requires the Regulated Ectodomain Cleavage of Neuronal Pentraxin NPR by TACE. / Cho, Richard W.; Park, Joo Min; Wolff, Steffen B E; Xu, Desheng; Hopf, Carsten; Kim, Jin ah; Reddy, Radhika C.; Petralia, Ronald S.; Perin, Mark S.; Linden, David J; Worley, Paul F.

In: Neuron, Vol. 57, No. 6, 27.03.2008, p. 858-871.

Research output: Contribution to journalArticle

Cho, RW, Park, JM, Wolff, SBE, Xu, D, Hopf, C, Kim, JA, Reddy, RC, Petralia, RS, Perin, MS, Linden, DJ & Worley, PF 2008, 'mGluR1/5-Dependent Long-Term Depression Requires the Regulated Ectodomain Cleavage of Neuronal Pentraxin NPR by TACE', Neuron, vol. 57, no. 6, pp. 858-871. https://doi.org/10.1016/j.neuron.2008.01.010
Cho, Richard W. ; Park, Joo Min ; Wolff, Steffen B E ; Xu, Desheng ; Hopf, Carsten ; Kim, Jin ah ; Reddy, Radhika C. ; Petralia, Ronald S. ; Perin, Mark S. ; Linden, David J ; Worley, Paul F. / mGluR1/5-Dependent Long-Term Depression Requires the Regulated Ectodomain Cleavage of Neuronal Pentraxin NPR by TACE. In: Neuron. 2008 ; Vol. 57, No. 6. pp. 858-871.
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