Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acyltransferases / metabolism
-
Alanine / metabolism
-
Animals
-
Animals, Newborn
-
Binding Sites / physiology
-
Calcineurin / metabolism
-
Carrier Proteins / metabolism*
-
Cells, Cultured
-
Cytoskeletal Proteins
-
Dynamin I / metabolism*
-
Endocytosis / drug effects
-
Endocytosis / physiology*
-
Glutamic Acid / metabolism
-
Macromolecular Substances / metabolism
-
Mutagenesis, Site-Directed
-
Nerve Tissue Proteins / metabolism
-
Peptides / pharmacology
-
Phosphorylation / drug effects
-
Presynaptic Terminals / drug effects
-
Presynaptic Terminals / metabolism*
-
Protein Binding / physiology
-
Rats
-
Rats, Sprague-Dawley
-
Serine / metabolism
-
Synaptic Transmission / drug effects
-
Synaptic Transmission / physiology*
-
Synaptic Vesicles / drug effects
-
Synaptic Vesicles / metabolism*
-
Synaptosomes
Substances
-
Carrier Proteins
-
Cytoskeletal Proteins
-
Macromolecular Substances
-
Nerve Tissue Proteins
-
Pacsin1 protein, rat
-
Peptides
-
amphiphysin
-
Glutamic Acid
-
Serine
-
Acyltransferases
-
2-acylglycerophosphate acyltransferase
-
Calcineurin
-
Dynamin I
-
Alanine