@article{c5b272f6c80a4649ad2b111924193a85,
title = "mGluR1/5-Dependent Long-Term Depression Requires the Regulated Ectodomain Cleavage of Neuronal Pentraxin NPR by TACE",
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.",
keywords = "CELLBIO, MOLNEURO, SIGNALING",
author = "Cho, {Richard W.} and Park, {Joo Min} and Wolff, {Steffen B.E.} and Desheng Xu and Carsten Hopf and Kim, {Jin ah} and Reddy, {Radhika C.} and Petralia, {Ronald S.} and Perin, {Mark S.} and Linden, {David J.} and Worley, {Paul F.}",
note = "Funding Information: We thank Michael Chang, Sung Jin Park, and Jason Shepherd for helpful discussion on the manuscript as well as experimental design. We thank Maurice D. Hinson for technical assistance with NPR mutant constructs, Ya-Xian Wang for help with the immunogold studies, Roland Bock for cerebellum cultures, and Marlin H. Dehoff and Glory Harris for assistance with animal models. We also thank Yoko Sekine-Aizawa and Richard Huganir for providing BBS-tagged GluR1 and helpful discussion. This study was supported by National Institutes of Health grants 5R01NS039156-08 (P.F.W), R37MM51106 (D.J.L), and in part by the National Eye Institute's Visual Neuroscience Training Program (R.W.C.) and the National Institute on Deafness and Other Communication Disorders Intramural Program (R.S.P.). ",
year = "2008",
month = mar,
day = "27",
doi = "10.1016/j.neuron.2008.01.010",
language = "English (US)",
volume = "57",
pages = "858--871",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "6",
}