RGD Reference Report - Syndapin I and endophilin I bind overlapping proline-rich regions of dynamin I: role in synaptic vesicle endocytosis. - Rat Genome Database

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Syndapin I and endophilin I bind overlapping proline-rich regions of dynamin I: role in synaptic vesicle endocytosis.

Authors: Anggono, V  Robinson, PJ 
Citation: Anggono V and Robinson PJ, J Neurochem. 2007 Aug;102(3):931-43. Epub 2007 Apr 16.
RGD ID: 8554440
Pubmed: (View Article at PubMed) PMID:17437541
DOI: Full-text: DOI:10.1111/j.1471-4159.2007.04574.x

Dynamin I mediates vesicle fission during synaptic vesicle endocytosis (SVE). Its proline-rich domain (PRD) binds the Src-homology 3 (SH3) domain of a subset of proteins that can deform membranes. Syndapin I, amphiphysin I, and endophilin I are its major partners implicated in SVE. Syndapin binding is controlled by phosphorylation at Ser-774 and Ser-778 in the dynamin phospho-box. We now define syndapin and endophilin-binding sites by peptide competition and site-directed mutagenesis. Both bound the same region of the dynamin PRD and both exhibited unusual bidirectional binding modes around core PxxP motifs, unlike amphiphysin which employed a class II binding mode. Endophilin binds to tandem PxxP motifs in the sequence (778)SPTPQRRAPAVPPARPGSR(796) in dynamin, with SPTPQ being an overhang sequence. In contrast, syndapin binding involves two components in the region (772)RRSPTSSPTPQRRAPAVPPARPGSR(796). It required a single PxxP core and a non-PxxP N-terminally anchored extension which bridges the phospho-box and may contribute to binding specificity and affinity. Syndapin binding is exquisitely sensitive to the introduction of negative charges almost anywhere along this region, explaining why it is a highly tuned phospho-sensor. Over-expression of dynamin point mutants that fail to bind syndapin or endophilin inhibit SVE in cultured neurons. Due to overlapping binding sites the interactions between dynamin and syndapin or endophilin were mutually exclusive. Because syndapin acts as a phospho-sensor, this supports its role in depolarization-induced SVE at the synapse, which involves dynamin dephosphorylation. We propose syndapin and endophilin function either at different stages during SVE or in mechanistically distinct types of SVE.

Annotation

Gene Ontology Annotations    

Biological Process

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Amph  (amphiphysin)
Dnm1  (dynamin 1)
Grb2  (growth factor receptor bound protein 2)
Pacsin1  (protein kinase C and casein kinase substrate in neurons 1)
Pik3r1  (phosphoinositide-3-kinase regulatory subunit 1)
Sh3gl2  (SH3 domain containing GRB2 like 2, endophilin A1)


Additional Information