Recruitment of Jub by α-catenin promotes Yki activity and Drosophila wing growth

ABSTRACT The Hippo signaling network controls organ growth through YAP family transcription factors, including the Drosophila Yorkie protein. YAP activity is responsive to both biochemical and biomechanical cues, with one key input being tension within the F-actin cytoskeleton. Several potential mechanisms for the biomechanical regulation of YAP proteins have been described, including tension-dependent recruitment of Ajuba family proteins, which inhibit kinases that inactivate YAP proteins, to adherens junctions. Here, we investigate the mechanism by which the Drosophila Ajuba family protein Jub is recruited to adherens junctions, and the contribution of this recruitment to the regulation of Yorkie. We identify α-catenin as the mechanotransducer responsible for tension-dependent recruitment of Jub by identifying a region of α-catenin that associates with Jub, and by identifying a region, which when deleted, allows constitutive, tension-independent recruitment of Jub. We also show that increased Jub recruitment to α-catenin is associated with increased Yorkie activity and wing growth, even in the absence of increased cytoskeletal tension. Our observations establish α-catenin as a multi-functional mechanotransducer and confirm Jub recruitment to α-catenin as a key contributor to biomechanical regulation of Hippo signaling. Highlighted Article: Identification of α-catenin as the mechanotransducer that recruits Jub to junctions under tension; this recruitment of Jub is sufficient to increase Yorkie activity.

• Publication year

  2019

• Venue

  Journal of Cell Science

• Publication date

  2019-01-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1242/jcs.222018PMID 30659113PMCID PMC6432719
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Salt bridges gate α-catenin activation at intercellular junctions

  2018cited by this paper
• The Hippo Signaling Network and Its Biological Functions.

  2018cited by this paper
• Mechanosensing and Mechanotransduction at Cell-Cell Junctions.

  2018cited by this paper
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  2017cited by this paper
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  2017cited by this paper
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  2016cited by this paper
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  2016cited by this paper
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  2015cited by this paper
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  2015influential reference
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  2015cited by this paper
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  2015cited by this paper
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  2015cited by this paper
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  2015cited by this paper
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  2014cited by this paper
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  2014cited by this paper
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  2014cited by this paper
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  2013cited by this paper
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  2013cited by this paper
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  2012cited by this paper
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  2011influential reference
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  2011cited by this paper
• α-Catenin as a tension transducer that induces adherens junction development

  2010influential reference
• In vivo regulation of Yorkie phosphorylation and localization

  2008cited by this paper
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  2007cited by this paper
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  2006cited by this paper
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  2004cited by this paper
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  2003influential reference
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  2003cited by this paper
• Drosophila Rho-associated kinase (Drok) links Frizzled-mediated planar cell polarity signaling to the actin cytoskeleton.

  2001cited by this paper
• Phosphorylation and Activation of Myosin by Rho-associated Kinase (Rho-kinase)*

  1996cited by this paper

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  2023cites this paper
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  2023cites this paper
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  2023cites this paper
• The Interaction of Mechanics and the Hippo Pathway in Drosophila melanogaster

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  2022cites this paper
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  2022cites this paper
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  2022cites this paper
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  2022cites this paper
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  2022cites this paper
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  2022cites this paper
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  2022cites this paper
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  2021cites this paper
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  2021cites this paper
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• Mechanosensing in embryogenesis.

  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2019cites this paper
• Control of cellular responses to mechanical cues through YAP/TAZ regulation

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  2019cites this paper
• Force transduction by cadherin adhesions in morphogenesis

  2019cites this paper