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

Prathamesh T. Nadar-Ponniah; Shahar Taiber; Michal Caspi; Tal Koffler-Brill; Amiel A. Dror; Ronen Siman-Tov; Moran Rubinstein; Krishnanand Padmanabhan; Chen Luxenburg; Richard A. Lang; Karen B. Avraham; Rina Rosin-Arbesfeld

doi:10.3389/fcell.2020.00615

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

Prathamesh T. Nadar-Ponniah, Shahar Taiber, Michal Caspi, Tal Koffler-Brill, Amiel A. Dror, Ronen Siman-Tov, Moran Rubinstein, Krishnanand Padmanabhan, Chen Luxenburg, Richard A. Lang, Karen B. Avraham, Rina Rosin-Arbesfeld

Bar-Ilan University - Azrieli Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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 adhesion. Since the cell junctions are 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. Additionally, striatin-deficient mice show aberrant ribbon synapse maturation. Loss of the outer hair cells, combined with the aberrant ribbon synapse distribution, may lead to the observed auditory impairment. Together, these results suggest a novel function for striatin in the mammalian auditory system.

Original language	English
Article number	615
Journal	Frontiers in Cell and Developmental Biology
Volume	8
DOIs	https://doi.org/10.3389/fcell.2020.00615
State	Published - 15 Jul 2020

Bibliographical note

Publisher Copyright:
© Copyright © 2020 Nadar-Ponniah, Taiber, Caspi, Koffler-Brill, Dror, Siman-Tov, Rubinstein, Padmanabhan, Luxenburg, Lang, Avraham and Rosin-Arbesfeld.

Funding

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). Funding. The research was supported by a US-Israel Binational Science Foundation grant 2017173 (RR-A), National Institutes of Health/NIDCD R01DC011835 (KA), and a Cincinnati Children’s Hospital Medical Center – Tel Aviv University Sackler Faculty of Medicine Grant for Collaborative Research (RL and RR-A).

Funders	Funder number
National Institutes of Health
National Institute on Deafness and Other Communication Disorders	R01DC011835
Cincinnati Children's Hospital Medical Center
United States-Israel Binational Science Foundation	2017173

Keywords

STRIPAK
cell junctions
deafness
hearing loss
striatin

Access to Document

10.3389/fcell.2020.00615

Cite this

Nadar-Ponniah, P. T., Taiber, S., Caspi, M., Koffler-Brill, T., Dror, A. A., Siman-Tov, R., Rubinstein, M., Padmanabhan, K., Luxenburg, C., Lang, R. A., Avraham, K. B., & Rosin-Arbesfeld, R. (2020). Striatin Is Required for Hearing and Affects Inner Hair Cells and Ribbon Synapses. Frontiers in Cell and Developmental Biology, 8, Article 615. https://doi.org/10.3389/fcell.2020.00615

@article{6a30365a37e447c492f02fc4b054cfe1,

title = "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 adhesion. Since the cell junctions are 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. Additionally, striatin-deficient mice show aberrant ribbon synapse maturation. Loss of the outer hair cells, combined with the aberrant ribbon synapse distribution, may lead to the observed auditory impairment. Together, these results suggest a novel function for striatin in the mammalian auditory system.",

keywords = "STRIPAK, cell junctions, deafness, hearing loss, striatin",

author = "Nadar-Ponniah, {Prathamesh T.} and Shahar Taiber and Michal Caspi and Tal Koffler-Brill and Dror, {Amiel A.} and Ronen Siman-Tov and Moran Rubinstein and Krishnanand Padmanabhan and Chen Luxenburg and Lang, {Richard A.} and Avraham, {Karen B.} and Rina Rosin-Arbesfeld",

note = "Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Nadar-Ponniah, Taiber, Caspi, Koffler-Brill, Dror, Siman-Tov, Rubinstein, Padmanabhan, Luxenburg, Lang, Avraham and Rosin-Arbesfeld.",

year = "2020",

month = jul,

day = "15",

doi = "10.3389/fcell.2020.00615",

language = "אנגלית",

volume = "8",

journal = "Frontiers in Cell and Developmental Biology",

issn = "2296-634X",

publisher = "Frontiers Media SA",

}

TY - JOUR

T1 - Striatin Is Required for Hearing and Affects Inner Hair Cells and Ribbon Synapses

AU - Nadar-Ponniah, Prathamesh T.

AU - Taiber, Shahar

AU - Caspi, Michal

AU - Koffler-Brill, Tal

AU - Dror, Amiel A.

AU - Siman-Tov, Ronen

AU - Rubinstein, Moran

AU - Padmanabhan, Krishnanand

AU - Luxenburg, Chen

AU - Lang, Richard A.

AU - Avraham, Karen B.

AU - Rosin-Arbesfeld, Rina

PY - 2020/7/15

Y1 - 2020/7/15

N2 - 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 adhesion. Since the cell junctions are 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. Additionally, striatin-deficient mice show aberrant ribbon synapse maturation. Loss of the outer hair cells, combined with the aberrant ribbon synapse distribution, may lead to the observed auditory impairment. Together, these results suggest a novel function for striatin in the mammalian auditory system.

AB - 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 adhesion. Since the cell junctions are 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. Additionally, striatin-deficient mice show aberrant ribbon synapse maturation. Loss of the outer hair cells, combined with the aberrant ribbon synapse distribution, may lead to the observed auditory impairment. Together, these results suggest a novel function for striatin in the mammalian auditory system.

KW - STRIPAK

KW - cell junctions

KW - deafness

KW - hearing loss

KW - striatin

UR - http://www.scopus.com/inward/record.url?scp=85088787133&partnerID=8YFLogxK

U2 - 10.3389/fcell.2020.00615

DO - 10.3389/fcell.2020.00615

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 32766247

AN - SCOPUS:85088787133

SN - 2296-634X

VL - 8

JO - Frontiers in Cell and Developmental Biology

JF - Frontiers in Cell and Developmental Biology

M1 - 615

ER -

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

Abstract

Bibliographical note

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Cite this