Cell- and stimulus-dependent heterogeneity of synaptic vesicle endocytic recycling mechanisms revealed by studies of dynamin 1-null neurons

Mitsuko Hayashi, Andrea Raimondi, Eileen O'Toole, Summer Paradise, Chiara Collesi, Ottavio Cremona, Shawn M. Ferguson, Pietro De Camilli

Research output: Contribution to journalArticle

Abstract

Mice lacking expression of dynamin 1, a GTPase implicated in the fission reaction of synaptic vesicle endocytosis, fail to thrive and exhibit severe activity-dependent endocytic defects at their synapses. Here, we have used electron tomography to investigate the massive increase in clathrin-coated pit abundance that is selectively observed at a subset of synapses in dynamin 1 KO primary neuron cultures under conditions of spontaneous network activity. This increase, leading to branched tubular plasma membrane invaginations capped by clathrin-coated buds, occurs selectively at inhibitory synapses. A similar massive increase of clathrin-coated profiles (in this case, of clathrin-coated vesicles) is observed at inhibitory synapses of neurons that lack expression of synaptojanin 1, a phosphoinositide phosphatase involved in clathrin-coated vesicle uncoating. Thus, although excitatory synapses are largely spared under these conditions, inhibitory synapses are uniquely sensitive to perturbation of endocytic proteins, probably as a result of their higher levels of tonic activity leading to a buildup of clathrin-coated intermediates in these synapses. In contrast, the predominant endocytic structures observed at the majority of dynamin 1 KO synapses after acute stimulation are endosome-like intermediates that originate by a dynamin 1-independent form of endocytosis. These findings reveal a striking heterogeneity in the mode of synaptic vesicle recycling in different synapses and functional states.

Original languageEnglish
Pages (from-to)2175-2180
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number6
DOIs
Publication statusPublished - Feb 12 2008

Keywords

  • Clathrin
  • Electron microscopy
  • Endocytosis
  • Synapse
  • Synaptojanin

ASJC Scopus subject areas

  • Genetics
  • General

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