A dynamin 1-, dynamin 3- and clathrin-independent pathway of synaptic vesicle recycling mediated by bulk endocytosis

Elife. 2014 Jun 24;3:e01621. doi: 10.7554/eLife.01621.


The exocytosis of synaptic vesicles (SVs) elicited by potent stimulation is rapidly compensated by bulk endocytosis of SV membranes leading to large endocytic vacuoles ('bulk' endosomes). Subsequently, these vacuoles disappear in parallel with the reappearance of new SVs. We have used synapses of dynamin 1 and 3 double knock-out neurons, where clathrin-mediated endocytosis (CME) is dramatically impaired, to gain insight into the poorly understood mechanisms underlying this process. Massive formation of bulk endosomes was not defective, but rather enhanced, in the absence of dynamin 1 and 3. The subsequent conversion of bulk endosomes into SVs was not accompanied by the accumulation of clathrin coated buds on their surface and this process proceeded even after further clathrin knock-down, suggesting its independence of clathrin. These findings support the existence of a pathway for SV reformation that bypasses the requirement for clathrin and dynamin 1/3 and that operates during intense synaptic activity.

Keywords: endosome; exocytosis; high pressure freezing; synaptic transmission; syndapin.

Publication types

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

MeSH terms

  • Animals
  • Clathrin / deficiency
  • Clathrin / genetics*
  • Dynamin I / deficiency
  • Dynamin I / genetics*
  • Dynamin III / deficiency
  • Dynamin III / genetics*
  • Embryo, Mammalian
  • Endocytosis / genetics*
  • Endosomes / metabolism
  • Exocytosis / genetics
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology
  • Neurons / metabolism*
  • Primary Cell Culture
  • Synapses / genetics
  • Synapses / metabolism
  • Synaptic Transmission
  • Synaptic Vesicles / metabolism*


  • Clathrin
  • Nerve Tissue Proteins
  • Dynamin I
  • Dynamin III