Intrinsic planar polarity mechanisms influence the position-dependent regulation of synapse properties in inner hair cells.
Proc Natl Acad Sci U S A 2019 Apr 30; 116(18):9084-9094
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 Gαi 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 Gαi 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 Gαi3 and LGN/Gpsm2 also disrupted the modiolar-pillar gradient of ribbon size. We propose a role for Gαi 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.
Jean, Philippe; Özçete, Özge Demet; Tarchini, Basile; and Moser, Tobias, "Intrinsic planar polarity mechanisms influence the position-dependent regulation of synapse properties in inner hair cells." (2019). Faculty Research 2019. 103.