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

Thomas Frank, Mark A. Rutherford, Nicola Strenzke, Andreas Neef, Tina Pangršič, Darina Khimich, Anna Fetjova, Eckart D. Gundelfinger, M. Charles Liberman, Benjamin Harke, Keith E. Bryan, Amy Lee, Alexander Egner, Dietmar Riedel, Tobias Moser

Research output: Contribution to journalArticlepeer-review

182 Scopus citations

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.

Original languageEnglish
Pages (from-to)724-738
Number of pages15
JournalNeuron
Volume68
Issue number4
DOIs
StatePublished - Nov 18 2010

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