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Overlapping role of dynamin isoforms in synaptic vesicle endocytosis.

The existence of neuron-specific endocytic protein isoforms raises questions about their importance for specialized neuronal functions. Dynamin, a GTPase implicated in the fission reaction of endocytosis, is encoded by three genes, two of which, dynamin 1 and 3, are highly expressed in neurons. We show that dynamin 3, thought to play a predominantly postsynaptic role, has a major presynaptic function. Although lack of dynamin 3 does not produce an overt phenotype in mice, it worsens the dynamin 1 KO phenotype, leading to perinatal lethality and a more severe defect in activity-dependent synaptic vesicle endocytosis. Thus, dynamin 1 and 3, which together account for the overwhelming majority of brain dynamin, cooperate in supporting optimal rates of synaptic vesicle endocytosis. Persistence of synaptic transmission in their absence indicates that if dynamin plays essential functions in neurons, such functions can be achieved by the very low levels of dynamin 2.

Pubmed ID: 21689597

Authors

  • Raimondi A
  • Ferguson SM
  • Lou X
  • Armbruster M
  • Paradise S
  • Giovedi S
  • Messa M
  • Kono N
  • Takasaki J
  • Cappello V
  • O'Toole E
  • Ryan TA
  • De Camilli P

Journal

Neuron

Publication Data

June 23, 2011

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK45735
  • Agency: NINDS NIH HHS, Id: NS36942
  • Agency: NIDA NIH HHS, Id: P30 DA018343
  • Agency: NIDA NIH HHS, Id: P30 DA018343-01
  • Agency: NIDDK NIH HHS, Id: P30 DK045735
  • Agency: NIDDK NIH HHS, Id: P30 DK045735-10
  • Agency: NCRR NIH HHS, Id: P41 RR000592
  • Agency: NCRR NIH HHS, Id: P41 RR000592-38
  • Agency: NINDS NIH HHS, Id: R01 NS036942
  • Agency: NINDS NIH HHS, Id: R01 NS036942-12
  • Agency: NINDS NIH HHS, Id: R37 NS036251
  • Agency: NINDS NIH HHS, Id: R37 NS036251-16
  • Agency: NINDS NIH HHS, Id: R37NS036251
  • Agency: NCRR NIH HHS, Id: RR-000592
  • Agency: Canadian Institutes of Health Research, Id:

Mesh Terms

  • Animals
  • Brain
  • Cells, Cultured
  • Dynamin I
  • Dynamin III
  • Endocytosis
  • Mice
  • Mice, Knockout
  • Neurons
  • Protein Isoforms
  • Synaptic Vesicles