Back to Search
Start Over
Neto1 associates with the NMDA receptor/amyloid precursor protein complex.
- Source :
- Journal of Neurochemistry; Sep2013, Vol. 126 Issue 5, p554-564, 11p, 11 Graphs
- Publication Year :
- 2013
-
Abstract
- Neuropilin tolloid-like 1 (Neto1), is a CUB domain-containing transmembrane protein that was recently identified as a novel component of the NMDA receptor complex. Here, we have investigated the possible association of Neto1 with the amyloid precursor protein ( APP)695/GluN1/GluN2A and APP695/GluN1/GluN2B NMDA receptor trafficking complexes that we have previously identified. Neto1 <superscript>HA</superscript> was shown to co-immunoprecipitate with assembled NMDA receptors via GluN2A or GluN2B subunits; Neto1 <superscript>HA</superscript> did not co-immunoprecipitate APP695 <superscript>FLAG</superscript>. Co-immunoprecipitations from mammalian cells co-transfected with APP695 <superscript>FLAG</superscript>, Neto1 <superscript>HA</superscript> and GluN1/GluN2A or GluN1/GluN2B revealed that all four proteins co-exist within one macromolecular complex. Immunoprecipitations from native brain tissue similarly revealed the existence of a GluN1/GluN2A or GluN2B/ APP/Neto1 complex. Neto1 <superscript>HA</superscript> caused a reduction in the surface expression of both NMDA receptor subtypes, but had no effect on APP695 <superscript>FLAG</superscript>- or PSD-95α<superscript>c-Myc</superscript> enhanced surface receptor expression. The Neto1 binding domain of GluN2A was mapped using GluN1/GluN2A chimeras and GluN2A truncation constructs. The extracellular GluN2A domain does not contribute to association with Neto1 <superscript>HA</superscript> but deletion of the intracellular tail resulted in a loss of Neto-1 <superscript>HA</superscript> co-immunoprecipitation which was paralleled by a loss of association between GluN2A and SAP102. Thus, Neto1 is concluded to be a component of APP/ NMDA receptor trafficking complexes. [ABSTRACT FROM AUTHOR]
- Subjects :
- PROTEIN precursors
CHEMICAL precursors
PROINSULIN
ZYMOGENS
INVOLUCRIN
Subjects
Details
- Language :
- English
- ISSN :
- 00223042
- Volume :
- 126
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Journal of Neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 89888185
- Full Text :
- https://doi.org/10.1111/jnc.12280