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Intrinsic planar polarity mechanisms influence the position-dependent regulation of synapse properties in inner hair cells.


ABSTRACT: Encoding the wide range of audible sounds in the mammalian cochlea is collectively achieved by functionally diverse type I spiral ganglion neurons (SGNs) at each tonotopic position. The firing of each SGN is thought to be driven by an individual active zone (AZ) of a given inner hair cell (IHC). These AZs present distinct properties according to their position within the IHC, to some extent forming a gradient between the modiolar and the pillar IHC side. In this study, we investigated whether signaling involved in planar polarity at the apical surface can influence position-dependent AZ properties at the IHC base. Specifically, we tested the role of G?i proteins and their binding partner LGN/Gpsm2 implicated in cytoskeleton polarization and hair cell (HC) orientation along the epithelial plane. Using high and superresolution immunofluorescence microscopy as well as patch-clamp combined with confocal Ca2+ imaging we analyzed IHCs in which G?i signaling was blocked by Cre-induced expression of the pertussis toxin catalytic subunit (PTXa). PTXa-expressing IHCs exhibited larger CaV1.3 Ca2+-channel clusters and consequently greater Ca2+ influx at the whole-cell and single-synapse levels, which also showed a hyperpolarized shift of activation. Moreover, PTXa expression collapsed the modiolar-pillar gradients of ribbon size and maximal synaptic Ca2+ influx. Finally, genetic deletion of G?i3 and LGN/Gpsm2 also disrupted the modiolar-pillar gradient of ribbon size. We propose a role for G?i proteins and LGN in regulating the position-dependent AZ properties in IHCs and suggest that this signaling pathway contributes to setting up the diverse firing properties of SGNs.

SUBMITTER: Jean P 

PROVIDER: S-EPMC6500111 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Intrinsic planar polarity mechanisms influence the position-dependent regulation of synapse properties in inner hair cells.

Jean Philippe P   Özçete Özge Demet ÖD   Tarchini Basile B   Moser Tobias T  

Proceedings of the National Academy of Sciences of the United States of America 20190411 18


Encoding the wide range of audible sounds in the mammalian cochlea is collectively achieved by functionally diverse type I spiral ganglion neurons (SGNs) at each tonotopic position. The firing of each SGN is thought to be driven by an individual active zone (AZ) of a given inner hair cell (IHC). These AZs present distinct properties according to their position within the IHC, to some extent forming a gradient between the modiolar and the pillar IHC side. In this study, we investigated whether si  ...[more]

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