Neuron
Volume 68, Issue 4, 18 November 2010, Pages 724-738
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Article
Bassoon and the Synaptic Ribbon Organize Ca2+ Channels and Vesicles to Add Release Sites and Promote Refilling

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Summary

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.

Highlights

► Few membrane-tethered synaptic vesicles upon Bassoon disruption, fewer without ribbon ► Ribbon promotes clustering of Ca2+ channels at the synapse ► Altered Ca2+ channel gating in mutants but Ca2+ coupling to exocytosis unaffected ► Synaptic transmission is impaired by fewer release sites and their slowed refilling

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These authors contributed equally to the work