RGD Reference Report - Role of the proline-rich domain of dynamin-2 and its interactions with Src homology 3 domains during endocytosis of the AT1 angiotensin receptor. - Rat Genome Database

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Role of the proline-rich domain of dynamin-2 and its interactions with Src homology 3 domains during endocytosis of the AT1 angiotensin receptor.

Authors: Szaszak, M  Gaborik, Z  Turu, G  McPherson, PS  Clark, AJ  Catt, KJ  Hunyady, L 
Citation: Szaszak M, etal., J Biol Chem 2002 Jun 14;277(24):21650-6.
RGD ID: 728683
Pubmed: PMID:11925437   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M200778200   (Journal Full-text)

In nonneural tissues, the dynamin-2 isoform participates in the formation of clathrin-coated vesicles during receptor endocytosis. In this study, the mechanism of dynamin-2 action was explored during endocytosis of the G protein-coupled AT1A angiotensin receptor expressed in Chinese hamster ovary cells. Dynamin-2 molecules with mutant pleckstrin homology domains or deleted proline-rich domains (PRD) exerted dominant negative inhibition on the endocytosis of radiolabeled angiotensin II. However, only the PRD mutation interfered with the localization of the dynamin-2 molecule to clathrin-coated pits and reduced the inhibitory effect of the GTPase-deficient K44A mutant dynamin-2. Green fluorescent protein-tagged Src homology 3 (SH3) domains of endophilin I and amphiphysin II, two major binding partners of dynamins, also inhibited AT1A receptor-mediated endocytosis of angiotensin II. These effects were partially or fully, respectively, restored by the overexpression of dynamin-2. Transient overexpression of these SH3 domains also reduced the localization of dynamin-2 to clathrin-coated pits. These data indicate that, similar to the recruitment of dynamin-1 during the recycling of synaptic vesicles, interaction of the dynamin-2 PRD with SH3 domains of proteins such as the amphiphysins and endophilins is essential for AT1A receptor endocytosis. This mechanism could be of general importance in dynamin-dependent endocytosis of other G protein-coupled receptors in nonneural tissues.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of clathrin-dependent endocytosis  IMP 728683 RGD 
receptor-mediated endocytosis  IDA 728683 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
clathrin-coated endocytic vesicle  IDA 728683 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dnm2  (dynamin 2)

Objects referenced in this article
Gene Agtr1b angiotensin II receptor, type 1b Rattus norvegicus

Additional Information