RGD Reference Report - Amphiphysin heterodimers: potential role in clathrin-mediated endocytosis. - Rat Genome Database

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Amphiphysin heterodimers: potential role in clathrin-mediated endocytosis.

Authors: Wigge, P  Kohler, K  Vallis, Y  Doyle, CA  Owen, D  Hunt, SP  McMahon, HT 
Citation: Wigge P, etal., Mol Biol Cell 1997 Oct;8(10):2003-15.
RGD ID: 631926
Pubmed: PMID:9348539   (View Abstract at PubMed)
PMCID: PMC25662   (View Article at PubMed Central)

Amphiphysin (Amph) is a src homology 3 domain-containing protein that has been implicated in synaptic vesicle endocytosis as a result of its interaction with dynamin. In a screen for novel members of the amphiphysin family, we identified Amph2, an isoform 49% identical to the previously characterized Amph1 protein. The subcellular distribution of this isoform parallels Amph1, both being enriched in nerve terminals. Like Amph1, a role in endocytosis at the nerve terminal is supported by the rapid dephosphorylation of Amph2 on depolarization. Importantly, the two isoforms can be coimmunoprecipitated from the brain as an equimolar complex, suggesting that the two isoforms act in concert. As determined by cross-linking of brain extracts, the Amph1-Amph2 complex is a 220- to 250-kDa heterodimer. COS cells transfected with either Amph1 or Amph2 show greatly reduced transferrin uptake, but coexpression of the two proteins rescues this defect, supporting a role for the heterodimer in clathrin-mediated endocytosis. Although the src homology 3 domains of both isoforms interact with dynamin, the heterodimer can associate with multiple dynamin molecules in vitro and activates dynamin's GTPase activity. We propose that it is an amphiphysin heterodimer that drives the recruitment of dynamin to clathrin-coated pits in endocytosing nerve terminals.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
axon terminus  IDA 631926; 631926 RGD 
cerebellar mossy fiber  IDA 631926 RGD 
extrinsic component of synaptic vesicle membrane is_active_inIDA 631926PMID:9348539SynGO 
glutamatergic synapse is_active_inIDA 631926PMID:9348539SynGO 
synaptic vesicle  IDA 631926 RGD 
varicosity  IDA 631926 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Amph  (amphiphysin)
Bin1  (bridging integrator 1)
Dnm1  (dynamin 1)


Additional Information