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Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription
The Hippo (Hpo) pathway regulates tissue growth in many animals. Multiple upstream components promote Hpo 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 (Kib) ac...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895526/ https://www.ncbi.nlm.nih.gov/pubmed/33555257 http://dx.doi.org/10.7554/eLife.62326 |
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author | Tokamov, Sherzod A Su, Ting Ullyot, Anne Fehon, Richard G |
author_facet | Tokamov, Sherzod A Su, Ting Ullyot, Anne Fehon, Richard G |
author_sort | Tokamov, Sherzod A |
collection | PubMed |
description | The Hippo (Hpo) pathway regulates tissue growth in many animals. Multiple upstream components promote Hpo 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 (Kib) activates the Hpo pathway by recruiting the core Hpo kinase cassette to the apical cortex. Here, we show that the Hpo pathway downregulates Drosophila Kib levels independently of Yorkie-mediated transcription. We find that Hpo signaling complex formation promotes Kib degradation via SCF(Slimb)-mediated ubiquitination, that this effect requires Merlin, Salvador, Hpo, and Warts, and that this mechanism functions independently of other upstream Hpo pathway activators. Moreover, Kib degradation appears patterned by differences in mechanical tension across the wing. We propose that Kib degradation mediated by Hpo pathway components and regulated by cytoskeletal tension serves to control Kib-driven Hpo pathway activation and ensure optimally scaled and patterned tissue growth. |
format | Online Article Text |
id | pubmed-7895526 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-78955262021-02-22 Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription Tokamov, Sherzod A Su, Ting Ullyot, Anne Fehon, Richard G eLife Cell Biology The Hippo (Hpo) pathway regulates tissue growth in many animals. Multiple upstream components promote Hpo 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 (Kib) activates the Hpo pathway by recruiting the core Hpo kinase cassette to the apical cortex. Here, we show that the Hpo pathway downregulates Drosophila Kib levels independently of Yorkie-mediated transcription. We find that Hpo signaling complex formation promotes Kib degradation via SCF(Slimb)-mediated ubiquitination, that this effect requires Merlin, Salvador, Hpo, and Warts, and that this mechanism functions independently of other upstream Hpo pathway activators. Moreover, Kib degradation appears patterned by differences in mechanical tension across the wing. We propose that Kib degradation mediated by Hpo pathway components and regulated by cytoskeletal tension serves to control Kib-driven Hpo pathway activation and ensure optimally scaled and patterned tissue growth. eLife Sciences Publications, Ltd 2021-02-08 /pmc/articles/PMC7895526/ /pubmed/33555257 http://dx.doi.org/10.7554/eLife.62326 Text en © 2021, Tokamov et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Tokamov, Sherzod A Su, Ting Ullyot, Anne Fehon, Richard G Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription |
title | Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription |
title_full | Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription |
title_fullStr | Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription |
title_full_unstemmed | Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription |
title_short | Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription |
title_sort | negative feedback couples hippo pathway activation with kibra degradation independent of yorkie-mediated transcription |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895526/ https://www.ncbi.nlm.nih.gov/pubmed/33555257 http://dx.doi.org/10.7554/eLife.62326 |
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