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Bassoon and the synaptic ribbon organize Ca²+ channels and vesicles to add release sites and promote refilling.

At the presynaptic active zone, Ca²+ influx triggers fusion of synaptic vesicles. It is not well understood how Ca²+ channel clustering and synaptic vesicle docking are organized. Here, we studied structure and function of hair cell ribbon synapses following genetic disruption of the presynaptic scaffold protein Bassoon. Mutant synapses--mostly lacking the ribbon--showed a reduction in membrane-proximal vesicles, with ribbonless synapses affected more than ribbon-occupied synapses. Ca²+ channels were also fewer at mutant synapses and appeared in abnormally shaped clusters. Ribbon absence reduced Ca²+ channel numbers at mutant and wild-type synapses. Fast and sustained exocytosis was reduced, notwithstanding normal coupling of the remaining Ca²+ channels to exocytosis. In vitro recordings revealed a slight impairment of vesicle replenishment. Mechanistic modeling of the in vivo data independently supported morphological and functional in vitro findings. We conclude that Bassoon and the ribbon (1) create a large number of release sites by organizing Ca²+ channels and vesicles, and (2) promote vesicle replenishment.

Pubmed ID: 21092861

Authors

  • Frank T
  • Rutherford MA
  • Strenzke N
  • Neef A
  • Pangršič T
  • Khimich D
  • Fejtova A
  • Fetjova A
  • Gundelfinger ED
  • Liberman MC
  • Harke B
  • Bryan KE
  • Lee A
  • Egner A
  • Riedel D
  • Moser T

Journal

Neuron

Publication Data

November 18, 2010

Associated Grants

  • Agency: NIDCD NIH HHS, Id: DC009433
  • Agency: NHLBI NIH HHS, Id: HL087120
  • Agency: NIDCD NIH HHS, Id: P30 DC005209
  • Agency: NIDCD NIH HHS, Id: R01 DC000188
  • Agency: NIDCD NIH HHS, Id: R01 DC009433
  • Agency: NIDCD NIH HHS, Id: R01 DC009433-04
  • Agency: NHLBI NIH HHS, Id: R01 HL087120
  • Agency: NHLBI NIH HHS, Id: R01 HL087120-03
  • Agency: NIAID NIH HHS, Id: T32 AI007260-20
  • Agency: NIAID NIH HHS, Id: T32 AI07260

Mesh Terms

  • Animals
  • Calcium Channels
  • Excitatory Postsynaptic Potentials
  • Exocytosis
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins
  • Neuronal Plasticity
  • Synapses
  • Synaptic Vesicles