Recruitment of Jub by α-catenin promotes Yki activity and <i>Drosophila</i> wing growth

Alégot, Hervé; Markosian, Christopher; Rauskolb, Cordelia; Yang, Janice; Kirichenko, Elmira; Wang, Yu-Chiun; Irvine, Kenneth D.

doi:10.1242/jcs.222018

Cited by 41 publications

(67 citation statements)

References 37 publications

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“…Ajuba is a LIM domain scaffold protein that is known to be recruited to adherens junctions through its association with α-Catenin (Marie et al, 2003). Increasing tension mediated by cytoskeleton in Drosophila wing discs recruits Warts to adherens junctions by Ajuba in a tension-dependent manner, which can suppress Warts activity and hence lead to activation of Yki downstream genes (Rauskolb et al, 2014;Alegot et al, 2019). This scenario supports the idea that mechanical force may stimulate cell proliferation in cell cultures (Boggiano and Fehon, 2012;McClatchey and Yap, 2012).…”

Section: Cell-cell Contact and The Hippo Pathwaysupporting

confidence: 65%

Hippo Signaling-Mediated Mechanotransduction in Cell Movement and Cancer Metastasis

Chang

Wang

et al. 2020

Front. Mol. Biosci.

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The evolutionarily conserved Hippo kinase signaling cascade governs cell proliferation, tissue differentiation and organ size, and can promote tumor growth and cancer metastasis when dysregulated. Unlike conventional signaling pathways driven by ligand-receptor binding to initiate downstream cascades, core Hippo kinases are activated not only by biochemical cues but also by mechanical ones generated from altered cell shape, cell polarity, cell-cell junctions or cell-extracellular matrix adhesion. In this review, we focus on recent advances showing how mechanical force acts through the actin cytoskeleton to regulate the Hippo pathway during cell movement and cancer invasion. We also discuss how this force affects YAP-dependent tissue growth and cell proliferation, and how disruption of that homeostatic relationship contributes to cancer metastasis.

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Section: Cell-cell Contact and The Hippo Pathwaysupporting

confidence: 65%

Hippo Signaling-Mediated Mechanotransduction in Cell Movement and Cancer Metastasis

Chang

Wang

et al. 2020

Front. Mol. Biosci.

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“…In particular, our data suggest that the M1 domain acts as a gatekeeper for Jub recruitment. In the absence of M1, junctional Jub levels become strikingly high, suggesting that M region mechanosensing has become ineffective in limiting Jub recruitment, causing Yki activation and overgrowth [see also Alegot et al, 2019].…”

Section: Discussionmentioning

confidence: 99%

“…Tension is thought to cause a conformational change in the M region and an unfurling of the M1 domain exposing a Vinc binding site [Yonemura et al, 2010;Ishiyama et al, 2013;Yao et al, 2014;Kim et al, 2015;Barrick et al, 2018]. However, Vinc is not required for limiting Jub recruitment indicating that either a second unknown binding partner of M1 or possibly an intramolecular interaction between M1 and the Jub binding site in the N domain [Marie et al, 2003;Alegot et al, 2019;this work] of normal levels. However, Jub increases to 119% without a noticeable increase in tissue size.…”

Section: Discussionmentioning

confidence: 99%

Role of α-Catenin and its mechanosensing properties in the regulation of Hippo/YAP-dependent tissue growth

Sarpal

Yan

Kazakova

et al. 2019

Preprint

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α-catenin is a key protein of adherens junctions (AJs) with mechanosensory properties. It also acts as a tumor suppressor that limits tissue growth. Here we analyzed the function of Drosophila α-Catenin (α-Cat) in growth regulation of the wing epithelium. We found that different α-Cat levels led to a differential activation of Hippo/Yorkie or JNK signaling causing tissue overgrowth or degeneration, respectively. α-Cat can modulate Yorkie-dependent tissue growth through recruitment of Ajuba, a negative regulator of Hippo signaling, to AJs but also through a mechanism that does not involve junctional recruitment of Ajuba. Further, both mechanosensory regions of α-Cat, the M region and the actin-binding domain (ABD), contribute to growth regulation. Whereas M is dispensable for α-Cat function in the wing, individual M domains (M1, M2, M3) have opposing effects on growth regulation. In particular, M1 limits Ajuba recruitment. Loss of M1 cause Ajuba hyper-recruitment to AJs promoting tissue-tension independent overgrowth. Although M1 binds Vinculin, Vinculin it is not responsible for this effect. Moreover, disruption of mechanosensing of the α-Cat actin-binding domain affects tissue growth, with enhanced actin interactions stabilizing junctions and leading to tissue overgrowth. Together, our findings indicate that α-Cat acts through multiple mechanisms to control tissue growth, including regulation of AJ stability, mechanosensitive Ajuba recruitment, and dynamic direct F-actin interactions.

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“…Both LIMD1 and VCL are recruited to an open form of a-catenin that is generated under tension (Alégot et al, 2019;Ibar et al, 2018;Yao et al, 2014;Yonemura et al, 2010). The requirement for TRIP6 in localization of LIMD1 and VCL to AJ thus implies that it is required to maintain this open form.…”

Section: Discussionmentioning

confidence: 99%

“…Localization of Ajuba family proteins to junctions requires a-catenin, and observations that Ajuba family proteins co-localize with and can co-precipitate a-catenin, together with identification of a-catenin mutations that constitutively recruit Jub, imply that they are recruited to junctions through interaction with a-catenin (Alégot et al, 2019;Ibar et al, 2018;Marie et al, 2003). As a-catenin undergoes a tension-dependent conformational change Yao et al, 2014;Yonemura et al, 2010), conformation-dependent binding to a-catenin could explain tension-dependent recruitment of Ajuba proteins (Alégot et al, 2019;Ibar et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

TRIP6 is required for tension at adherens junctions

Venkatramanan

Valenzuela

Irvine

2020

Preprint

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Hippo signaling mediates influences of cytoskeletal tension on organ growth. TRIP6and LIMD1 have each been identified as being required for tension-dependent inhibition of the Hippo pathway LATS kinases and their recruitment to adherens junctions, but the relationship between TRIP6 and LIMD1 was unknown. Using siRNA-mediated gene knockdown we show that TRIP6 is required for LIMD1 localization to adherens junctions, whereas LIMD1 is not required for TRIP6 localization. TRIP6, but not LIMD1, is also required for recruitment of Vinculin and VASP to adherens junctions. Knockdown of TRIP6 or Vinculin, but not of LIMD1, also influences the localization of phosphorylated myosin light chain and F-actin. In TRIP6 knockdown cells actin stress fibers are lost apically but increased basally, and there is a corresponding increase in recruitment of Vinculin and VASP to basal focal adhesions. These observations identify a role for TRIP6 in organizing F-actin and maintaining tension at adherens junctions that could account for its influence on LIMD1 and LATS. They also suggest that focal adhesions and adherens junctions compete for key proteins needed to maintain attachments to contractile F-actin.

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

Cited by 41 publications

References 37 publications

Hippo Signaling-Mediated Mechanotransduction in Cell Movement and Cancer Metastasis

Hippo Signaling-Mediated Mechanotransduction in Cell Movement and Cancer Metastasis

Role of α-Catenin and its mechanosensing properties in the regulation of Hippo/YAP-dependent tissue growth

TRIP6 is required for tension at adherens junctions

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