RGD Reference Report - Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission. - Rat Genome Database

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Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission.

Authors: Kittler, JT  Chen, G  Honing, S  Bogdanov, Y  McAinsh, K  Arancibia-Carcamo, IL  Jovanovic, JN  Pangalos, MN  Haucke, V  Yan, Z  Moss, SJ 
Citation: Kittler JT, etal., Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14871-6. Epub 2005 Sep 28.
RGD ID: 1601273
Pubmed: PMID:16192353   (View Abstract at PubMed)
PMCID: PMC1253579   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0506653102   (Journal Full-text)

The efficacy of synaptic inhibition depends on the number of gamma-aminobutyric acid type A receptors (GABA(A)Rs) expressed on the cell surface of neurons. The clathrin adaptor protein 2 (AP2) complex is a critical regulator of GABA(A)R endocytosis and, hence, surface receptor number. Here, we identify a previously uncharacterized atypical AP2 binding motif conserved within the intracellular domains of all GABA(A)R beta subunit isoforms. This AP2 binding motif (KTHLRRRSSQLK in the beta3 subunit) incorporates the major sites of serine phosphorylation within receptor beta subunits, and phosphorylation within this site inhibits AP2 binding. Furthermore, by using surface plasmon resonance, we establish that a peptide (pepbeta3) corresponding to the AP2 binding motif in the GABA(A)R beta3 subunit binds to AP2 with high affinity only when dephosphorylated. Moreover, the pepbeta3 peptide, but not its phosphorylated equivalent (pepbeta3-phos), enhanced the amplitude of miniature inhibitory synaptic current and whole cell GABA(A)R current. These effects of pepbeta3 on GABA(A)R current were occluded by inhibitors of dynamin-dependent endocytosis supporting an action of pepbeta3 on GABA(A)R endocytosis. Therefore phospho-dependent regulation of AP2 binding to GABA(A)Rs provides a mechanism to specify receptor cell surface number and the efficacy of inhibitory synaptic transmission.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gabrb3RatAP-2 adaptor complex binding  IPIAp2m1 (Rattus norvegicus) RGD 
Ap2m1Ratprotein binding  IPIGabrb3 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ap2m1  (adaptor related protein complex 2 subunit mu 1)
Gabrb3  (gamma-aminobutyric acid type A receptor subunit beta 3)


Additional Information