RGD Reference Report - A critical role for PSD-95/AKAP interactions in endocytosis of synaptic AMPA receptors. - Rat Genome Database

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A critical role for PSD-95/AKAP interactions in endocytosis of synaptic AMPA receptors.

Authors: Bhattacharyya, S  Biou, V  Xu, W  Schluter, O  Malenka, RC 
Citation: Bhattacharyya S, etal., Nat Neurosci. 2009 Feb;12(2):172-81. Epub 2009 Jan 25.
RGD ID: 2313185
Pubmed: PMID:19169250   (View Abstract at PubMed)
PMCID: PMC2694745   (View Article at PubMed Central)
DOI: DOI:10.1038/nn.2249   (Journal Full-text)

The endocytosis of AMPA receptors (AMPARs) underlies several forms of synaptic plasticity, including NMDA receptor (NMDAR)-dependent long-term depression (LTD), but the molecular mechanisms responsible for this trafficking remain unknown. We found that PSD-95, a major postsynaptic density protein, is important for NMDAR-triggered endocytosis of synaptic AMPARs in rat neuron cultures because of its binding to A kinase-anchoring protein 150 (AKAP150), a scaffold for specific protein kinases and phosphatases. Knockdown of PSD-95 with shRNA blocked NMDAR-triggered, but not constitutive or mGluR-triggered, endocytosis of AMPARs. Deletion of PSD-95's Src homology 3 and guanylate kinase-like domains, as well as a point mutation (L460P), both of which inhibit binding of PSD-95 to AKAP150, also blocked NMDAR-triggered AMPAR endocytosis. Furthermore, expression of a mutant AKAP150 that does not bind calcineurin inhibited this NMDAR-triggered trafficking event. Our results suggest that PSD-95's interaction with AKAP150 is critical for NMDAR-triggered AMPAR endocytosis and LTD, possibly because these scaffolds position calcineurin in the appropriate subsynaptic domain.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glutamatergic synapse is_active_inIDA 2313185PMID:19169250SynGO 
glutamatergic synapse is_active_inIMP 2313185PMID:19169250SynGO 

Objects Annotated

Genes (Rattus norvegicus)
Akap5  (A-kinase anchoring protein 5)


Additional Information