RGD Reference Report - Phosphorylation of the kainate receptor (KAR) auxiliary subunit Neto2 at serine 409 regulates synaptic targeting of the KAR subunit GluK1. - Rat Genome Database

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Phosphorylation of the kainate receptor (KAR) auxiliary subunit Neto2 at serine 409 regulates synaptic targeting of the KAR subunit GluK1.

Authors: Lomash, Richa Madan  Sheng, Nengyin  Li, Yan  Nicoll, Roger A  Roche, Katherine W 
Citation: Lomash RM, etal., J Biol Chem. 2017 Sep 15;292(37):15369-15377. doi: 10.1074/jbc.M117.787903. Epub 2017 Jul 17.
RGD ID: 155230759
Pubmed: PMID:28717010   (View Abstract at PubMed)
PMCID: PMC5602396   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M117.787903   (Journal Full-text)

Synaptic strength at excitatory synapses is determined by the presence of glutamate receptors (i.e. AMPA, NMDA, and kainate receptors) at the synapse. Synaptic strength is modulated by multiple factors including assembly of different receptor subunits, interaction with auxiliary subunits, and post-translational modifications of either the receptors or their auxiliary subunits. Using mass spectrometry, we found that the intracellular region of neuropilin and tolloid-like proteins (Neto) 1 and Neto2, the auxiliary subunits of kainate receptor (KARs), are phosphorylated by multiple kinases in vitro Specifically, Neto2 was phosphorylated at serine 409 (Ser-409) by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and protein kinase A (PKA) both in vitro and in heterologous cells. Interestingly, we observed a substantial increase in Neto2 Ser-409 phosphorylation in the presence of CaMKII, and this phosphorylation was reduced in the presence of the KAR subunit GluK1 or GluK2. We also found endogenous phosphorylation of Neto2 at Ser-409 in the brain. Moreover, Neto2 Ser-409 phosphorylation inhibited synaptic targeting of GluK1 because, unlike WT Neto2 and the phosphodeficient mutant Neto2 S409A, the Neto2 S409D phosphomimetic mutant impeded GluK1 trafficking to synapses. These results support a molecular mechanism by which Neto2 phosphorylation at Ser-409 helps restrict GluK1 targeting to the synapse.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Neto2Ratglutamatergic synapse is_active_inIDA PMID:28717010SynGO 
Neto2Ratglutamatergic synapse is_active_inIMP PMID:28717010SynGO 

Objects Annotated

Genes (Rattus norvegicus)
Neto2  (neuropilin and tolloid like 2)


Additional Information