title: Bassoon and the synaptic ribbon organize Ca²+ channels and vesicles to add release sites and promote refilling.
abstract: 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.
authors.affiliation: InnerEarLab, Department of Otolaryngology and Center for Molecular Physiology of the Brain, University of Göttingen Medical Center, 37099 Göttingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Frank
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rutherford
authors.forename: Nicola
authors.initials: N
authors.lastname: Strenzke
authors.forename: Andreas
authors.initials: A
authors.lastname: Neef
authors.forename: Tina
authors.initials: T
authors.lastname: Pangršič
authors.forename: Darina
authors.initials: D
authors.lastname: Khimich
authors.forename: Anna
authors.initials: A
authors.lastname: Fejtova
authors.forename: Anna
authors.initials: A
authors.lastname: Fetjova
authors.forename: Eckart D
authors.initials: ED
authors.lastname: Gundelfinger
authors.forename: M Charles
authors.initials: MC
authors.lastname: Liberman
authors.forename: Benjamin
authors.initials: B
authors.lastname: Harke
authors.forename: Keith E
authors.initials: KE
authors.lastname: Bryan
authors.forename: Amy
authors.initials: A
authors.lastname: Lee
authors.forename: Alexander
authors.initials: A
authors.lastname: Egner
authors.forename: Dietmar
authors.initials: D
authors.lastname: Riedel
authors.forename: Tobias
authors.initials: T
authors.lastname: Moser
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology*; D005089:Exocytosis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D013572:Synaptic Vesicles / Q000235:genetics / Q000502:physiology*
chemical_list: C498441:Bsn protein, mouse; D015220:Calcium Channels; D009419:Nerve Tissue Proteins