Complexes of Usher proteins preassemble at the endoplasmic reticulum and are required for trafficking and ER homeostasis

Usher syndrome (USH), the leading cause of hereditary combined hearing and vision loss, is characterized by sensorineural deafness and progressive retinal degeneration. Mutations in several different genes produce USH, but the proximal cause of sensory cell death remains mysterious. We adapted a pro...

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Main Authors:	Blanco-Sánchez, Bernardo, Clément, Aurélie, Fierro, Javier, Washbourne, Philip, Westerfield, Monte
Format:	Online
Language:	English
Published:	The Company of Biologists Limited 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007406/

id	pubmed-4007406
recordtype	oai_dc
spelling	pubmed-40074062014-05-14 Complexes of Usher proteins preassemble at the endoplasmic reticulum and are required for trafficking and ER homeostasis Blanco-Sánchez, Bernardo Clément, Aurélie Fierro, Javier Washbourne, Philip Westerfield, Monte Research Article Usher syndrome (USH), the leading cause of hereditary combined hearing and vision loss, is characterized by sensorineural deafness and progressive retinal degeneration. Mutations in several different genes produce USH, but the proximal cause of sensory cell death remains mysterious. We adapted a proximity ligation assay to analyze associations among three of the USH proteins, Cdh23, Harmonin and Myo7aa, and the microtubule-based transporter Ift88 in zebrafish inner ear mechanosensory hair cells. We found that the proteins are in close enough proximity to form complexes and that these complexes preassemble at the endoplasmic reticulum (ER). Defects in any one of the three USH proteins disrupt formation and trafficking of the complex and result in diminished levels of the other proteins, generalized trafficking defects and ER stress that triggers apoptosis. ER stress, thus, contributes to sensory hair cell loss and provides a new target to explore for protective therapies for USH. The Company of Biologists Limited 2014-05 2014-03-13 /pmc/articles/PMC4007406/ /pubmed/24626987 http://dx.doi.org/10.1242/dmm.014068 Text en © 2014. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Blanco-Sánchez, Bernardo Clément, Aurélie Fierro, Javier Washbourne, Philip Westerfield, Monte
spellingShingle	Blanco-Sánchez, Bernardo Clément, Aurélie Fierro, Javier Washbourne, Philip Westerfield, Monte Complexes of Usher proteins preassemble at the endoplasmic reticulum and are required for trafficking and ER homeostasis
author_facet	Blanco-Sánchez, Bernardo Clément, Aurélie Fierro, Javier Washbourne, Philip Westerfield, Monte
author_sort	Blanco-Sánchez, Bernardo
title	Complexes of Usher proteins preassemble at the endoplasmic reticulum and are required for trafficking and ER homeostasis
title_short	Complexes of Usher proteins preassemble at the endoplasmic reticulum and are required for trafficking and ER homeostasis
title_full	Complexes of Usher proteins preassemble at the endoplasmic reticulum and are required for trafficking and ER homeostasis
title_fullStr	Complexes of Usher proteins preassemble at the endoplasmic reticulum and are required for trafficking and ER homeostasis
title_full_unstemmed	Complexes of Usher proteins preassemble at the endoplasmic reticulum and are required for trafficking and ER homeostasis
title_sort	complexes of usher proteins preassemble at the endoplasmic reticulum and are required for trafficking and er homeostasis
description	Usher syndrome (USH), the leading cause of hereditary combined hearing and vision loss, is characterized by sensorineural deafness and progressive retinal degeneration. Mutations in several different genes produce USH, but the proximal cause of sensory cell death remains mysterious. We adapted a proximity ligation assay to analyze associations among three of the USH proteins, Cdh23, Harmonin and Myo7aa, and the microtubule-based transporter Ift88 in zebrafish inner ear mechanosensory hair cells. We found that the proteins are in close enough proximity to form complexes and that these complexes preassemble at the endoplasmic reticulum (ER). Defects in any one of the three USH proteins disrupt formation and trafficking of the complex and result in diminished levels of the other proteins, generalized trafficking defects and ER stress that triggers apoptosis. ER stress, thus, contributes to sensory hair cell loss and provides a new target to explore for protective therapies for USH.
publisher	The Company of Biologists Limited
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007406/
_version_	1612084490172104704

Complexes of Usher proteins preassemble at the endoplasmic reticulum and are required for trafficking and ER homeostasis

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