Nature Neuroscience 9, 752 - 760 (2006)
Published online: 30 April 2006; | doi:10.1038/nn1695
Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosisVictor Anggono1, Karen J Smillie2, Mark E Graham1, Valentina A Valova1, Michael A Cousin2
& Phillip J Robinson11
Cell Signalling Unit, Children's Medical Research Institute, Locked Bag 23, Wentworthville, NSW 2145, Australia. 2
Membrane Biology Group, Centre for Integrative Physiology, George Square, University of Edinburgh, EH8 9XD, Scotland, UK.
Correspondence should be addressed to Phillip J Robinson phrobins@mail.usyd.edu.au Dynamin I is dephosphorylated at Ser-774 and Ser-778 during synaptic vesicle endocytosis (SVE) in nerve terminals. Phosphorylation was proposed to regulate the assembly of an endocytic protein complex with amphiphysin or endophilin. Instead, we found it recruits syndapin I for SVE and does not control amphiphysin or endophilin binding in rat synaptosomes. After depolarization, syndapin showed a calcineurin-mediated interaction with dynamin. A peptide mimicking the phosphorylation sites disrupted the dynamin-syndapin complex, not the dynamin-endophilin complex, arrested SVE and produced glutamate release fatigue after repetitive stimulation. Pseudophosphorylation of Ser-774 or Ser-778 inhibited syndapin binding without affecting amphiphysin recruitment. Site mutagenesis to alanine arrested SVE in cultured neurons. The effects of the sites were additive for syndapin I binding and SVE. Thus syndapin I is a central component of the endocytic protein complex for SVE via stimulus-dependent recruitment to dynamin I and has a key role in synaptic transmission.
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