Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning.
| Autor: | 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 |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | PLoS Biology, Vol 7, Iss 2, p e41 (2009) |
| Druh dokumentu: | article |
| ISSN: | 1544-9173 1545-7885 |
| DOI: | 10.1371/journal.pbio.1000041 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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