Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning.

The N-methyl-D-aspartate receptor (NMDAR), a major excitatory ligand-gated ion channel in the central nervous system (CNS), is a principal mediator of synaptic plasticity. Here we report that neuropilin tolloid-like 1 (Neto1), a complement C1r/C1s, Uegf, Bmp1 (CUB) domain-containing transmembrane pr...

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Autores principales:	David Ng, Graham M Pitcher, Rachel K Szilard, Andréa Sertié, Marijana Kanisek, Steven J Clapcote, Tatiana Lipina, Lorraine V Kalia, Daisy Joo, Colin McKerlie, Miguel Cortez, John C Roder, Michael W Salter, Roderick R McInnes
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3b93d0508888458dabaff426a1a4130a
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spelling	oai:doaj.org-article:3b93d0508888458dabaff426a1a4130a2021-11-25T05:33:47ZNeto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning.1544-91731545-788510.1371/journal.pbio.1000041https://doaj.org/article/3b93d0508888458dabaff426a1a4130a2009-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19243221/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885The N-methyl-D-aspartate receptor (NMDAR), a major excitatory ligand-gated ion channel in the central nervous system (CNS), is a principal mediator of synaptic plasticity. Here we report that neuropilin tolloid-like 1 (Neto1), a complement C1r/C1s, Uegf, Bmp1 (CUB) domain-containing transmembrane protein, is a novel component of the NMDAR complex critical for maintaining the abundance of NR2A-containing NMDARs in the postsynaptic density. Neto1-null mice have depressed long-term potentiation (LTP) at Schaffer collateral-CA1 synapses, with the subunit dependency of LTP induction switching from the normal predominance of NR2A- to NR2B-NMDARs. NMDAR-dependent spatial learning and memory is depressed in Neto1-null mice, indicating that Neto1 regulates NMDA receptor-dependent synaptic plasticity and cognition. Remarkably, we also found that the deficits in LTP, learning, and memory in Neto1-null mice were rescued by the ampakine CX546 at doses without effect in wild-type. Together, our results establish the principle that auxiliary proteins are required for the normal abundance of NMDAR subunits at synapses, and demonstrate that an inherited learning defect can be rescued pharmacologically, a finding with therapeutic implications for humans.David NgGraham M PitcherRachel K SzilardAndréa SertiéMarijana KanisekSteven J ClapcoteTatiana LipinaLorraine V KaliaDaisy JooColin McKerlieMiguel CortezJohn C RoderMichael W SalterRoderick R McInnesPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 7, Iss 2, p e41 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 David Ng Graham M Pitcher Rachel K Szilard Andréa Sertié Marijana Kanisek Steven J Clapcote Tatiana Lipina Lorraine V Kalia Daisy Joo Colin McKerlie Miguel Cortez John C Roder Michael W Salter Roderick R McInnes Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning.
description	The N-methyl-D-aspartate receptor (NMDAR), a major excitatory ligand-gated ion channel in the central nervous system (CNS), is a principal mediator of synaptic plasticity. Here we report that neuropilin tolloid-like 1 (Neto1), a complement C1r/C1s, Uegf, Bmp1 (CUB) domain-containing transmembrane protein, is a novel component of the NMDAR complex critical for maintaining the abundance of NR2A-containing NMDARs in the postsynaptic density. Neto1-null mice have depressed long-term potentiation (LTP) at Schaffer collateral-CA1 synapses, with the subunit dependency of LTP induction switching from the normal predominance of NR2A- to NR2B-NMDARs. NMDAR-dependent spatial learning and memory is depressed in Neto1-null mice, indicating that Neto1 regulates NMDA receptor-dependent synaptic plasticity and cognition. Remarkably, we also found that the deficits in LTP, learning, and memory in Neto1-null mice were rescued by the ampakine CX546 at doses without effect in wild-type. Together, our results establish the principle that auxiliary proteins are required for the normal abundance of NMDAR subunits at synapses, and demonstrate that an inherited learning defect can be rescued pharmacologically, a finding with therapeutic implications for humans.
format	article
author	David Ng Graham M Pitcher Rachel K Szilard Andréa Sertié Marijana Kanisek Steven J Clapcote Tatiana Lipina Lorraine V Kalia Daisy Joo Colin McKerlie Miguel Cortez John C Roder Michael W Salter Roderick R McInnes
author_facet	David Ng Graham M Pitcher Rachel K Szilard Andréa Sertié Marijana Kanisek Steven J Clapcote Tatiana Lipina Lorraine V Kalia Daisy Joo Colin McKerlie Miguel Cortez John C Roder Michael W Salter Roderick R McInnes
author_sort	David Ng
title	Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning.
title_short	Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning.
title_full	Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning.
title_fullStr	Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning.
title_full_unstemmed	Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning.
title_sort	neto1 is a novel cub-domain nmda receptor-interacting protein required for synaptic plasticity and learning.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/3b93d0508888458dabaff426a1a4130a
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Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning.

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