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Neuron. 2008 Mar 27;57(6):858-71. doi: 10.1016/j.neuron.2008.01.010.

mGluR1/5-dependent long-term depression requires the regulated ectodomain cleavage of neuronal pentraxin NPR by TACE.

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1
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

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-alpha 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.

PMID:
18367087
PMCID:
PMC2701195
DOI:
10.1016/j.neuron.2008.01.010
[Indexed for MEDLINE]
Free PMC Article

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