Striatin is required for hearing and affects inner hair cells and ribbon synapses

Abstract

Striatin, a subunit of the serine/threonine phosphatase PP2A, is a core member of the conserved striatin-interacting phosphatase and kinase (STRIPAK) complexes. The protein is expressed in the cell junctions between epithelial cells, which play a role in maintaining cell-cell junctional integrity. Since adhesion is crucial for the function of the mammalian inner ear, we examined the localization and function of striatin in the mouse cochlea. Our results show that in neonatal mice, striatin is specifically expressed in the cell-cell junctions of the inner hair cells, the receptor cells in the mammalian cochlea.Auditory brainstem response measurements of striatin-deficient mice indicated a progressive, high-frequency hearing loss, suggesting that striatin is essential for normal hearing. Moreover, scanning electron micrographs of the organ of Corti revealed a moderate degeneration of the outer hair cells in the middle and basal regions, concordant with the high-frequency hearing loss. Importantly, striatin-deficient mice show aberrant ribbon synapse maturation that may lead to the observed auditory impairment. Together, these results suggest a novel function for striatin in the mammalian auditory system. Medicine Grant for Collaborative Research (RL, RRA). We thank Ana Turchetti-Maia and Kevin Ohlemiller for their advice for EP recordings, Vered Holdengreber for help with electron microscopy, and Ronen Siman-Tov for help with the mice. Author contributions KBA and RRA conceived the project. RAL generated the Striatin knockout mice. PTNP designed and performed the genotyping, dissections of inner ears, ABR, SEM, confocal imaging, Western blots, and quantification of ribbon synapses. MR and ST performed the endocochlear potential experiments. ST and TK-B aided with dissections and SEM imaging analysis. MC and AAD aided with image analysis, experimental design and organizing the data. PTNP, ST, KBA, and RRA wrote the manuscript. KBA and RRA supervised the work.

gEAR: Gene Expression Analysis Resource portal for community-driven, multi-omic data exploration

“…High-profile, hearingrelated datasets have been made available in the gEAR even before publication, and links to gEAR as the primary method for accessing datasets are ubiquitous within talks/posters at professional conferences. Additionally, the gEAR has already been used for data dissemination 5,[23][24][25][26][27][28][29][30][31][32][33][34][35] , hypothesis generation [36][37][38][39][40][41][42][43][44] and validation of gene expression 29,30,[45][46][47][48][49][50][51][52][53][54][55][56][57] by numerous publications in the ear field. It has also been referenced by numerous groups as a useful tool [58][59][60][61][62][63][64] .…”

gEAR: gene Expression Analysis Resource portal for community-driven, multi-omic data exploration

“…High-profile, hearingrelated datasets have been made available in the gEAR even before publication, and links to gEAR as the primary method for accessing datasets are ubiquitous within talks/posters at professional conferences. Additionally, the gEAR has already been used for data dissemination 5,[23][24][25][26][27][28][29][30][31][32][33][34][35] , hypothesis generation [36][37][38][39][40][41][42][43][44] and validation of gene expression 29,30,[45][46][47][48][49][50][51][52][53][54][55][56][57] by numerous publications in the ear field. It has also been referenced by numerous groups as a useful tool [58][59][60][61][62][63][64] .…”

Striatin Is Required for Hearing and Affects Inner Hair Cells and Ribbon Synapses

“…We thank Ana Turchetti-Maia and Kevin Ohlemiller for their advice for EP recordings and Vered Holdengreber for help with electron microscopy. This manuscript has been released as a pre-print at bioRxiv (Nadar Ponniah et al, 2020).…”