The E3 ligase Ubr3 regulates Usher syndrome and MYH9 disorder proteins in the auditory organs of Drosophila and mammals

Tongchao Li; Nikolaos Giagtzoglou; Daniel F Eberl; Sonal Nagarkar Jaiswal; Tiantian Cai; Dorothea Godt; Andrew K Groves; Hugo J Bellen

doi:10.7554/eLife.15258

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The E3 ligase Ubr3 regulates Usher syndrome and MYH9 disorder proteins in the auditory organs of Drosophila and mammals

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The E3 ligase Ubr3 regulates Usher syndrome and MYH9 disorder proteins in the auditory organs of Drosophila and mammals

Tongchao Li, Nikolaos Giagtzoglou, Daniel F Eberl, Sonal Nagarkar Jaiswal, Tiantian Cai, Dorothea Godt, Andrew K Groves and Hugo J Bellen

eLife, Vol.5, e15258

06/22/2016

DOI: 10.7554/eLife.15258

PMCID: PMC4978524

PMID: 27331610

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Abstract

Myosins play essential roles in the development and function of auditory organs and multiple myosin genes are associated with hereditary forms of deafness. Using a forward genetic screen in Drosophila, we identified an E3 ligase, Ubr3, as an essential gene for auditory organ development. Ubr3 negatively regulates the mono-ubiquitination of non-muscle Myosin II, a protein associated with hearing loss in humans. The mono-ubiquitination of Myosin II promotes its physical interaction with Myosin VIIa, a protein responsible for Usher syndrome type IB. We show that ubr3 mutants phenocopy pathogenic variants of Myosin II and that Ubr3 interacts genetically and physically with three Usher syndrome proteins. The interactions between Myosin VIIa and Myosin IIa are conserved in the mammalian cochlea and in human retinal pigment epithelium cells. Our work reveals a novel mechanism that regulates protein complexes affected in two forms of syndromic deafness and suggests a molecular function for Myosin IIa in auditory organs.

Cell Line

Cochlea - embryology

Animals

Genetic Testing

Drosophila

Humans

Ubiquitin-Protein Ligases - metabolism

Myosins - metabolism

Drosophila Proteins - genetics

Drosophila Proteins - metabolism

Ubiquitin-Protein Ligases - genetics

Nonmuscle Myosin Type IIA - metabolism

Details

Title: Subtitle: The E3 ligase Ubr3 regulates Usher syndrome and MYH9 disorder proteins in the auditory organs of Drosophila and mammals
Creators: Tongchao Li - Baylor College of Medicine
Nikolaos Giagtzoglou - Baylor College of Medicine
Daniel F Eberl - Department of Biology, University of Iowa, Iowa City, United States
Sonal Nagarkar Jaiswal - Baylor College of Medicine
Tiantian Cai - Department of Neuroscience, Baylor College of Medicine, Houston, United States
Dorothea Godt - Department of Cell and Systems Biology, University of Toronto, Toronto, Canada
Andrew K Groves - Department of Neuroscience, Baylor College of Medicine, Houston, United States
Hugo J Bellen - Department of Neuroscience, Baylor College of Medicine, Houston, United States
Resource Type: Journal article
Publication Details: eLife, Vol.5, e15258
DOI: 10.7554/eLife.15258
PMID: 27331610
PMCID: PMC4978524
NLM abbreviation: Elife
ISSN: 2050-084X
eISSN: 2050-084X
Publisher: England
Grant note: P30 HD024064 / NICHD NIH HHS Howard Hughes Medical Institute P30 DC010362 / NIDCD NIH HHS R21 DC010987 / NIDCD NIH HHS
Language: English
Date published: 06/22/2016
Academic Unit: Iowa Neuroscience Institute; Biology
Record Identifier: 9983991990402771

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