Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription

  1. Sherzod A Tokamov
  2. Ting Su
  3. Anne Ullyot
  4. Richard G Fehon  Is a corresponding author
  1. University of Chicago, United States
  2. UT Southwestern Medical Center, United States

Abstract

The Hippo pathway regulates tissue growth in many animals. Multiple upstream components promote Hippo pathway activity, but the organization of these different inputs, the degree of crosstalk between them, and whether they are regulated in a distinct manner is not well understood. Kibra activates the Hippo pathway by recruiting the core Hippo kinase cassette to the apical cortex. Here we show that the Hippo pathway downregulates Drosophila Kibra levels independently of Yorkie-mediated transcription. We find that Hippo signaling complex formation promotes Kibra degradation via SCFSlimb-mediated ubiquitination, that this effect requires Merlin, Salvador, Hippo, and Warts, and that this mechanism functions independently of other upstream Hippo pathway activators. Moreover, Kibra degradation appears patterned by differences in mechanical tension across the wing. We propose that Kibra degradation mediated by Hippo pathway components and regulated by cytoskeletal tension serves to control Kibra-driven Hippo pathway activation and ensure optimally scaled and patterned tissue growth.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Sherzod A Tokamov

    Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Ting Su

    Department of Physiology, UT Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1124-517X
  3. Anne Ullyot

    Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Richard G Fehon

    Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United States
    For correspondence
    rfehon@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4889-2602

Funding

National Institute of Neurological Disorders and Stroke (NS034783)

  • Richard G Fehon

National Institute of General Medical Sciences (T32 GM007183)

  • Sherzod A Tokamov

National Science Foundation (Graduate Research Fellowship)

  • Sherzod A Tokamov

S. A. T. conceptualized the project, performed most of the experiments and data collection, and wrote the manuscript. R. G. F. conceptualized supervised all aspects of the project, and helped writing the manuscript. Both S. A. T. and R. G. F. agreed to submit the work for publication.

Reviewing Editor

  1. Elisabeth Knust, Max-Planck Institute of Molecular Cell Biology and Genetics, Germany

Publication history

  1. Received: August 21, 2020
  2. Accepted: February 8, 2021
  3. Accepted Manuscript published: February 8, 2021 (version 1)
  4. Version of Record published: February 19, 2021 (version 2)

Copyright

© 2021, Tokamov 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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  1. Sherzod A Tokamov
  2. Ting Su
  3. Anne Ullyot
  4. Richard G Fehon
(2021)
Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription
eLife 10:e62326.
https://doi.org/10.7554/eLife.62326

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