RGD Reference Report - PIKE-mediated PI3-kinase activity is required for AMPA receptor surface expression. - Rat Genome Database

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PIKE-mediated PI3-kinase activity is required for AMPA receptor surface expression.

Authors: Chan, CB  Chen, Y  Liu, X  Tang, X  Lee, CW  Mei, L  Ye, K 
Citation: Chan CB, etal., EMBO J. 2011 Aug 16;30(20):4274-86. doi: 10.1038/emboj.2011.281.
RGD ID: 8553599
Pubmed: PMID:21847098   (View Abstract at PubMed)
PMCID: PMC3199380   (View Article at PubMed Central)
DOI: DOI:10.1038/emboj.2011.281   (Journal Full-text)

AMPAR (alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor) is an ion channel involved in the formation of synaptic plasticity. However, the molecular mechanism that couples plasticity stimuli to the trafficking of postsynaptic AMPAR remains poorly understood. Here, we show that PIKE (phosphoinositide 3-kinase enhancer) GTPases regulate neuronal AMPAR activity by promoting GluA2/GRIP1 association. PIKE-L directly interacts with both GluA2 and GRIP1 and forms a tertiary complex upon glycine-induced NMDA receptor activation. PIKE-L is also essential for glycine-induced GluA2-associated PI3K activation. Genetic ablation of PIKE (PIKE(-/-)) in neurons suppresses GluA2-associated PI3K activation, therefore inhibiting the subsequent surface expression of GluA2 and the formation of long-term potentiation. Our findings suggest that PIKE-L is a critical factor in controlling synaptic AMPAR insertion.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Agap2Ratcellular response to glycine  IDA  RGD 
Gria2Ratcellular response to glycine  IDA  RGD 
Agap2Ratphosphatidylinositol metabolic process  IMP  RGD 
Agap2Ratpositive regulation of protein localization to cell surface  IMP  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Agap2Ratdendrite  IDA MMO:0000686RGD 
Gria2Ratdendrite  IDA MMO:0000686RGD 
Grip1Ratdendrite  IDA MMO:0000686RGD 
Agap2Ratexternal side of plasma membrane  IDA MMO:0000686RGD 

Objects Annotated

Genes (Rattus norvegicus)
Agap2  (ArfGAP with GTPase domain, ankyrin repeat and PH domain 2)
Gria2  (glutamate ionotropic receptor AMPA type subunit 2)
Grip1  (glutamate receptor interacting protein 1)


Additional Information