PMID- 19243221
OWN - NLM
STAT- MEDLINE
DCOM- 20090507
LR  - 20220321
IS  - 1545-7885 (Electronic)
IS  - 1544-9173 (Print)
IS  - 1544-9173 (Linking)
VI  - 7
IP  - 2
DP  - 2009 Feb 24
TI  - Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for 
      synaptic plasticity and learning.
PG  - e41
LID - 10.1371/journal.pbio.1000041 [doi]
LID - e1000041
AB  - 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.
FAU - Ng, David
AU  - Ng D
AD  - Program in Developmental Biology, The Research Institute, Hospital for Sick 
      Children, Toronto, Ontario, Canada.
FAU - Pitcher, Graham M
AU  - Pitcher GM
FAU - Szilard, Rachel K
AU  - Szilard RK
FAU - Sertie, Andrea
AU  - Sertie A
FAU - Kanisek, Marijana
AU  - Kanisek M
FAU - Clapcote, Steven J
AU  - Clapcote SJ
FAU - Lipina, Tatiana
AU  - Lipina T
FAU - Kalia, Lorraine V
AU  - Kalia LV
FAU - Joo, Daisy
AU  - Joo D
FAU - McKerlie, Colin
AU  - McKerlie C
FAU - Cortez, Miguel
AU  - Cortez M
FAU - Roder, John C
AU  - Roder JC
FAU - Salter, Michael W
AU  - Salter MW
FAU - McInnes, Roderick R
AU  - McInnes RR
LA  - eng
GR  - Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - PLoS Biol
JT  - PLoS biology
JID - 101183755
RN  - 0 (1-(1,4-benzodioxan-6-ylcarbonyl)piperidine)
RN  - 0 (Dioxoles)
RN  - 0 (LDL-Receptor Related Proteins)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Membrane Proteins)
RN  - 0 (Neto1 protein, mouse)
RN  - 0 (Piperidines)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Dioxoles/pharmacology
MH  - Hippocampus/metabolism
MH  - Humans
MH  - LDL-Receptor Related Proteins
MH  - Learning/drug effects/*physiology
MH  - Lipoproteins, LDL/*metabolism
MH  - Long-Term Potentiation/drug effects/genetics
MH  - Male
MH  - Membrane Proteins/*metabolism
MH  - Memory/drug effects/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neuronal Plasticity/drug effects/*genetics
MH  - Piperidines/pharmacology
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Synaptic Transmission/drug effects/*genetics
PMC - PMC2652390
COIS- Competing interests. The authors have declared that no competing interests exist.
EDAT- 2009/02/27 09:00
MHDA- 2009/05/08 09:00
PMCR- 2009/02/24
CRDT- 2009/02/27 09:00
PHST- 2008/04/17 00:00 [received]
PHST- 2009/01/12 00:00 [accepted]
PHST- 2009/02/27 09:00 [entrez]
PHST- 2009/02/27 09:00 [pubmed]
PHST- 2009/05/08 09:00 [medline]
PHST- 2009/02/24 00:00 [pmc-release]
AID - 08-PLBI-RA-1527 [pii]
AID - 08-PLBI-RA-1527R3 [pii]
AID - 10.1371/journal.pbio.1000041 [doi]
PST - ppublish
SO  - PLoS Biol. 2009 Feb 24;7(2):e41. doi: 10.1371/journal.pbio.1000041.