A slowed classical pathway rather than kiss-and-run mediates endocytosis at synapses lacking synaptojanin and endophilin

Cell. 2005 Nov 4;123(3):521-33. doi: 10.1016/j.cell.2005.09.026.


The extent to which a "kiss-and-run" mode of endocytosis contributes to synaptic-vesicle recycling remains controversial. The only genetic evidence for kiss-and-run at the synapse comes from mutations in the genes encoding synaptojanin and endophilin, proteins that together function to uncoat vesicles in classical clathrin-mediated endocytosis. Here we have characterized the endocytosis that persists in null alleles of Drosophila synaptojanin and endophilin. In response to high-frequency stimulation, the synaptic-vesicle pool can be reversibly depleted in these mutants. Recovery from this depletion is slow and indicates the persistence of an impaired form of classical endocytosis. Steady-state exocytosis rates reveal that endocytosis saturates in mutant neuromuscular terminals at approximately 80 vesicles/s, 10%-20% of the wild-type rate. Analyses of quantal size, FM1-43 loading, and dynamin function further demonstrate that, even in the absence of synaptojanin or endophilin, vesicles undergo full fusion and re-formation. Therefore, no genetic evidence remains to indicate that synaptic vesicles undergo kiss-and-run.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyltransferases / genetics
  • Acyltransferases / metabolism*
  • Animals
  • Drosophila / genetics
  • Drosophila / physiology*
  • Drosophila / ultrastructure
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Dynamins / metabolism
  • Electric Stimulation
  • Endocytosis / physiology
  • Fluorescent Dyes
  • Microscopy, Electron, Transmission
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuromuscular Junction / physiology
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism*
  • Pyridinium Compounds
  • Quaternary Ammonium Compounds
  • Synapses / physiology*
  • Synapses / ultrastructure
  • Synaptic Vesicles / physiology
  • Synaptic Vesicles / ultrastructure


  • Drosophila Proteins
  • FM1 43
  • Fluorescent Dyes
  • Nerve Tissue Proteins
  • Pyridinium Compounds
  • Quaternary Ammonium Compounds
  • Acyltransferases
  • endophilin A, Drosophila
  • synaptojanin
  • Phosphoric Monoester Hydrolases
  • Dynamins