Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription
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.
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
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.
- Elisabeth Knust, Max-Planck Institute of Molecular Cell Biology and Genetics, Germany
- Received: August 21, 2020
- Accepted: February 8, 2021
- Accepted Manuscript published: February 8, 2021 (version 1)
- Version of Record published: February 19, 2021 (version 2)
© 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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