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Tryptophan-rich basic protein (WRB) mediates insertion of the tail-anchored protein otoferlin and is required for hair cell exocytosis and hearing

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Tryptophan-rich basic protein (WRB) mediates insertion of the tail-anchored protein otoferlin and is required for hair cell exocytosis and hearing. / Vogl, Christian; Panou, Iliana; Yamanbaeva, Gulnara; Wichmann, Carolin; Mangosing, Sara J; Vilardi, Fabio; Indzhykulian, Artur A; Pangršič, Tina; Santarelli, Rosamaria; Rodriguez-Ballesteros, Montserrat; Weber, Thomas; Jung, Sangyong; Cardenas, Elena; Wu, Xudong; Wojcik, Sonja M; Kwan, Kelvin Y; Del Castillo, Ignacio; Schwappach, Blanche; Strenzke, Nicola; Corey, David P; Lin, Shuh-Yow; Moser, Tobias.

in: EMBO J, Jahrgang 35, Nr. 23, 01.12.2016, S. 2536-2552.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Vogl, C, Panou, I, Yamanbaeva, G, Wichmann, C, Mangosing, SJ, Vilardi, F, Indzhykulian, AA, Pangršič, T, Santarelli, R, Rodriguez-Ballesteros, M, Weber, T, Jung, S, Cardenas, E, Wu, X, Wojcik, SM, Kwan, KY, Del Castillo, I, Schwappach, B, Strenzke, N, Corey, DP, Lin, S-Y & Moser, T 2016, 'Tryptophan-rich basic protein (WRB) mediates insertion of the tail-anchored protein otoferlin and is required for hair cell exocytosis and hearing', EMBO J, Jg. 35, Nr. 23, S. 2536-2552. https://doi.org/10.15252/embj.201593565

APA

Vogl, C., Panou, I., Yamanbaeva, G., Wichmann, C., Mangosing, S. J., Vilardi, F., Indzhykulian, A. A., Pangršič, T., Santarelli, R., Rodriguez-Ballesteros, M., Weber, T., Jung, S., Cardenas, E., Wu, X., Wojcik, S. M., Kwan, K. Y., Del Castillo, I., Schwappach, B., Strenzke, N., ... Moser, T. (2016). Tryptophan-rich basic protein (WRB) mediates insertion of the tail-anchored protein otoferlin and is required for hair cell exocytosis and hearing. EMBO J, 35(23), 2536-2552. https://doi.org/10.15252/embj.201593565

Vancouver

Vogl C, Panou I, Yamanbaeva G, Wichmann C, Mangosing SJ, Vilardi F et al. Tryptophan-rich basic protein (WRB) mediates insertion of the tail-anchored protein otoferlin and is required for hair cell exocytosis and hearing. EMBO J. 2016 Dez 1;35(23):2536-2552. https://doi.org/10.15252/embj.201593565

Bibtex

@article{0adb91d2bc6c49b4818773eea89198ff,
title = "Tryptophan-rich basic protein (WRB) mediates insertion of the tail-anchored protein otoferlin and is required for hair cell exocytosis and hearing",
abstract = "The transmembrane recognition complex (TRC40) pathway mediates the insertion of tail-anchored (TA) proteins into membranes. Here, we demonstrate that otoferlin, a TA protein essential for hair cell exocytosis, is inserted into the endoplasmic reticulum (ER) via the TRC40 pathway. We mutated the TRC40 receptor tryptophan-rich basic protein (Wrb) in hair cells of zebrafish and mice and studied the impact of defective TA protein insertion. Wrb disruption reduced otoferlin levels in hair cells and impaired hearing, which could be restored in zebrafish by transgenic Wrb rescue and otoferlin overexpression. Wrb-deficient mouse inner hair cells (IHCs) displayed normal numbers of afferent synapses, Ca2+ channels, and membrane-proximal vesicles, but contained fewer ribbon-associated vesicles. Patch-clamp of IHCs revealed impaired synaptic vesicle replenishment. In vivo recordings from postsynaptic spiral ganglion neurons showed a use-dependent reduction in sound-evoked spiking, corroborating the notion of impaired IHC vesicle replenishment. A human mutation affecting the transmembrane domain of otoferlin impaired its ER targeting and caused an auditory synaptopathy. We conclude that the TRC40 pathway is critical for hearing and propose that otoferlin is an essential substrate of this pathway in hair cells.",
keywords = "Animals, Arsenite Transporting ATPases/metabolism, Exocytosis, Gene Knockout Techniques, Genetic Complementation Test, Hair Cells, Auditory/metabolism, Hearing, Humans, Membrane Proteins/metabolism, Mice, Nuclear Proteins/genetics, Zebrafish, Zebrafish Proteins/genetics",
author = "Christian Vogl and Iliana Panou and Gulnara Yamanbaeva and Carolin Wichmann and Mangosing, {Sara J} and Fabio Vilardi and Indzhykulian, {Artur A} and Tina Pangr{\v s}i{\v c} and Rosamaria Santarelli and Montserrat Rodriguez-Ballesteros and Thomas Weber and Sangyong Jung and Elena Cardenas and Xudong Wu and Wojcik, {Sonja M} and Kwan, {Kelvin Y} and {Del Castillo}, Ignacio and Blanche Schwappach and Nicola Strenzke and Corey, {David P} and Shuh-Yow Lin and Tobias Moser",
note = "{\textcopyright} 2016 The Authors.",
year = "2016",
month = dec,
day = "1",
doi = "10.15252/embj.201593565",
language = "English",
volume = "35",
pages = "2536--2552",
journal = "EMBO J",
issn = "0261-4189",
publisher = "NATURE PUBLISHING GROUP",
number = "23",

}

RIS

TY - JOUR

T1 - Tryptophan-rich basic protein (WRB) mediates insertion of the tail-anchored protein otoferlin and is required for hair cell exocytosis and hearing

AU - Vogl, Christian

AU - Panou, Iliana

AU - Yamanbaeva, Gulnara

AU - Wichmann, Carolin

AU - Mangosing, Sara J

AU - Vilardi, Fabio

AU - Indzhykulian, Artur A

AU - Pangršič, Tina

AU - Santarelli, Rosamaria

AU - Rodriguez-Ballesteros, Montserrat

AU - Weber, Thomas

AU - Jung, Sangyong

AU - Cardenas, Elena

AU - Wu, Xudong

AU - Wojcik, Sonja M

AU - Kwan, Kelvin Y

AU - Del Castillo, Ignacio

AU - Schwappach, Blanche

AU - Strenzke, Nicola

AU - Corey, David P

AU - Lin, Shuh-Yow

AU - Moser, Tobias

N1 - © 2016 The Authors.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - The transmembrane recognition complex (TRC40) pathway mediates the insertion of tail-anchored (TA) proteins into membranes. Here, we demonstrate that otoferlin, a TA protein essential for hair cell exocytosis, is inserted into the endoplasmic reticulum (ER) via the TRC40 pathway. We mutated the TRC40 receptor tryptophan-rich basic protein (Wrb) in hair cells of zebrafish and mice and studied the impact of defective TA protein insertion. Wrb disruption reduced otoferlin levels in hair cells and impaired hearing, which could be restored in zebrafish by transgenic Wrb rescue and otoferlin overexpression. Wrb-deficient mouse inner hair cells (IHCs) displayed normal numbers of afferent synapses, Ca2+ channels, and membrane-proximal vesicles, but contained fewer ribbon-associated vesicles. Patch-clamp of IHCs revealed impaired synaptic vesicle replenishment. In vivo recordings from postsynaptic spiral ganglion neurons showed a use-dependent reduction in sound-evoked spiking, corroborating the notion of impaired IHC vesicle replenishment. A human mutation affecting the transmembrane domain of otoferlin impaired its ER targeting and caused an auditory synaptopathy. We conclude that the TRC40 pathway is critical for hearing and propose that otoferlin is an essential substrate of this pathway in hair cells.

AB - The transmembrane recognition complex (TRC40) pathway mediates the insertion of tail-anchored (TA) proteins into membranes. Here, we demonstrate that otoferlin, a TA protein essential for hair cell exocytosis, is inserted into the endoplasmic reticulum (ER) via the TRC40 pathway. We mutated the TRC40 receptor tryptophan-rich basic protein (Wrb) in hair cells of zebrafish and mice and studied the impact of defective TA protein insertion. Wrb disruption reduced otoferlin levels in hair cells and impaired hearing, which could be restored in zebrafish by transgenic Wrb rescue and otoferlin overexpression. Wrb-deficient mouse inner hair cells (IHCs) displayed normal numbers of afferent synapses, Ca2+ channels, and membrane-proximal vesicles, but contained fewer ribbon-associated vesicles. Patch-clamp of IHCs revealed impaired synaptic vesicle replenishment. In vivo recordings from postsynaptic spiral ganglion neurons showed a use-dependent reduction in sound-evoked spiking, corroborating the notion of impaired IHC vesicle replenishment. A human mutation affecting the transmembrane domain of otoferlin impaired its ER targeting and caused an auditory synaptopathy. We conclude that the TRC40 pathway is critical for hearing and propose that otoferlin is an essential substrate of this pathway in hair cells.

KW - Animals

KW - Arsenite Transporting ATPases/metabolism

KW - Exocytosis

KW - Gene Knockout Techniques

KW - Genetic Complementation Test

KW - Hair Cells, Auditory/metabolism

KW - Hearing

KW - Humans

KW - Membrane Proteins/metabolism

KW - Mice

KW - Nuclear Proteins/genetics

KW - Zebrafish

KW - Zebrafish Proteins/genetics

U2 - 10.15252/embj.201593565

DO - 10.15252/embj.201593565

M3 - SCORING: Journal article

C2 - 27458190

VL - 35

SP - 2536

EP - 2552

JO - EMBO J

JF - EMBO J

SN - 0261-4189

IS - 23

ER -