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

  1. Tongchao Li
  2. Nikolaos Giagtzoglou
  3. Dan Eberl
  4. Sonal Nagarkar-Jaiswal
  5. Tiantian Cai
  6. Dorothea Godt
  7. Andrew K Groves
  8. Hugo J Bellen  Is a corresponding author
  1. Baylor College of Medicine, United States
  2. Texas Children's Hospital, United States
  3. University of Iowa, United States
  4. University of Toronto, Canada
Research Article
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Cite this article as: eLife 2016;5:e15258 doi: 10.7554/eLife.15258

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.

Article and author information

Author details

  1. Tongchao Li

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  2. Nikolaos Giagtzoglou

    Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States
    Competing interests
    No competing interests declared.
  3. Dan Eberl

    Department of Biology, University of Iowa, Iowa City, United States
    Competing interests
    No competing interests declared.
  4. Sonal Nagarkar-Jaiswal

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  5. Tiantian Cai

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  6. Dorothea Godt

    Department of Cell and Systems Biology, University of Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.
  7. Andrew K Groves

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  8. Hugo J Bellen

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States
    For correspondence
    hbellen@bcm.edu
    Competing interests
    Hugo J Bellen, Reviewing editor, eLife.

Reviewing Editor

  1. K VijayRaghavan, Tata Institute of Fundamental Research, India

Publication history

  1. Received: February 15, 2016
  2. Accepted: June 21, 2016
  3. Accepted Manuscript published: June 22, 2016 (version 1)
  4. Version of Record published: July 20, 2016 (version 2)

Copyright

© 2016, Li et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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