Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosis.
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.
Anggono
Victor
V
Cell Signalling Unit, Children's Medical Research Institute, Locked Bag 23, Wentworthville, NSW 2145, Australia.
Smillie
Karen J
KJ
Graham
Mark E
ME
Valova
Valentina A
VA
Cousin
Michael A
MA
Robinson
Phillip J
PJ
D000217:Acyltransferases / Q000378:metabolism; D000409:Alanine / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites / Q000502:physiology; D019703:Calcineurin / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D034284:Dynamin I / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D046911:Macromolecular Substances / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; C117738:Pacsin1 protein, rat; D010455:Peptides; C075637:amphiphysin; D018698:Glutamic Acid; D012694:Serine; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase; D019703:Calcineurin; D034284:Dynamin I; D000409:Alanine