Cortical tension promotes Kibra degradation via Par-1.


Journal

Molecular biology of the cell
ISSN: 1939-4586
Titre abrégé: Mol Biol Cell
Pays: United States
ID NLM: 9201390

Informations de publication

Date de publication:
01 Jan 2024
Historique:
pubmed: 30 10 2023
medline: 30 10 2023
entrez: 30 10 2023
Statut: ppublish

Résumé

The Hippo pathway is an evolutionarily conserved regulator of tissue growth. Multiple Hippo signaling components are regulated via proteolytic degradation. However, how these degradation mechanisms are themselves modulated remains unexplored. Kibra is a key upstream pathway activator that promotes its own ubiquitin-mediated degradation upon assembling a Hippo signaling complex. Here, we demonstrate that Hippo complex-dependent Kibra degradation is modulated by cortical tension. Using classical genetic, osmotic, and pharmacological manipulations of myosin activity and cortical tension, we show that increasing cortical tension leads to Kibra degradation, whereas decreasing cortical tension increases Kibra abundance. Our study also implicates Par-1 in regulating Kib abundance downstream of cortical tension. We demonstrate that Par-1 promotes ubiquitin-mediated Kib degradation in a Hippo complex-dependent manner and is required for tension-induced Kib degradation. Collectively, our results reveal a previously unknown molecular mechanism by which cortical tension affects Hippo signaling and provide novel insights into the role of mechanical forces in growth control.

Identifiants

pubmed: 37903240
doi: 10.1091/mbc.E23-06-0246
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

ar2

Auteurs

Sherzod A Tokamov (SA)

Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637.
Committee on Development, Regeneration, and Stem Cell Biology, The University of Chicago, Chicago, IL 60637.

Stephan Buiter (S)

Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637.

Anne Ullyot (A)

Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637.

Gordana Scepanovic (G)

Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5G 1M1, Canada.

Audrey Miller Williams (AM)

Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637.

Rodrigo Fernandez-Gonzalez (R)

Institute of Biomedical Engineering and Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5G 1M1, Canada.

Sally Horne-Badovinac (S)

Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637.
Committee on Development, Regeneration, and Stem Cell Biology, The University of Chicago, Chicago, IL 60637.

Richard G Fehon (RG)

Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637.
Committee on Development, Regeneration, and Stem Cell Biology, The University of Chicago, Chicago, IL 60637.

Classifications MeSH