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

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

Blog Article

The N-methyl-D-aspartate receptor (NMDAR), a major excitatory JACKETS SPLIT SUIT BYRON 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 Sauce Pans 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.