The synaptic vesicle cycle: A single vesicle budding step involving clathrin and dynamin

Kohji Takei, Olaf Mundigl, Laurie Daniell, Pietro De Camilli

Research output: Contribution to journalArticlepeer-review

336 Citations (Scopus)


Strong evidence implicates clathrin-coated vesicles and endosome-like vacuoles in the reformation of synaptic vesicles after exocytosis, and it is generally assumed that these vacuoles represent a traffic station downstream from clathrin-coated vesicles. To gain insight into the mechanisms of synaptic vesicle budding from endosome-like intermediates, lysed nerve terminals and nerve terminal membrane subfractions were examined by EM after incubations with GTPγS. Numerous clathrin-coated budding intermediates that were positive for AP2 and AP180 immunoreactivity and often collared by a dynamin ring were seen. These were present not only on the plasma membrane (Takei, K., P.S. McPherson, S.L. Schmid, and P. De Camilli. 1995. Nature (Lond.). 374:186-190), but also on internal vacuoles. The lumen of these vacuoles retained extracellular tracers and was therefore functionally segregated from the extracellular medium, although narrow connections between their membranes and the plasmalemma were sometimes visible by serial sectioning. Similar observations were made in intact cultured hippocampal neurons exposed to high K+ stimulation. Coated vesicle buds were generally in the same size range of synaptic vesicles and positive for the synaptic vesicle protein synaptotagmin. Based on these results, we suggest that endosome-like intermediates of nerve terminals originate by bulk uptake of the plasma membrane and that clathrin- and dynamin-mediated budding takes place in parallel from the plasmalemma and from these internal membranes. We propose a synaptic vesicle recycling model that involves a single vesicle budding step mediated by clathrin and dynamin.

Original languageEnglish
Pages (from-to)1237-1250
Number of pages14
JournalJournal of Cell Biology
Issue number6
Publication statusPublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology


Dive into the research topics of 'The synaptic vesicle cycle: A single vesicle budding step involving clathrin and dynamin'. Together they form a unique fingerprint.

Cite this