Vesicle sub-pool organization at inner hair cell ribbon synapses.

Abstract:

:The afferent inner hair cell synapse harbors the synaptic ribbon, which ensures a constant vesicle supply. Synaptic vesicles (SVs) are arranged in morphologically discernable pools, linked via filaments to the ribbon or the presynaptic membrane. We propose that filaments play a major role in SV resupply and exocytosis at the ribbon. Using advanced electron microscopy, we demonstrate that SVs are organized in sub-pools defined by the filament number per vesicle and its connections. Upon stimulation, SVs increasingly linked to other vesicles and to the ribbon, whereas single-tethered SVs dominated at the membrane. Mutant mice for the hair cell protein otoferlin (pachanga, OtofPga/Pga ) are profoundly deaf with reduced sustained release, serving as a model to investigate the SV replenishment at IHCs. Upon stimulation, multiple-tethered and docked vesicles (rarely observed in wild-type) accumulated at OtofPga/Pga active zones due to an impairment downstream of docking. Conclusively, vesicles are organized in sub-pools at ribbon-type active zones by filaments to support vesicle supply, transport, and finally release.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Chakrabarti R,Michanski S,Wichmann C

doi

10.15252/embr.201744937

subject

Has Abstract

pub_date

2018-11-01 00:00:00

issue

11

eissn

1469-221X

issn

1469-3178

pii

embr.201744937

journal_volume

19

pub_type

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