Endocytosis-dependent coordination of multiple actin regulators is required for wound healing

Matsubayashi, Yutaka; Coulson-Gilmer, Camilla; Millard, Tom H.

doi:10.1083/jcb.201411037

Cited by 41 publications

(32 citation statements)

References 64 publications

(86 reference statements)

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“…The formation of the actomyosin cable depends on remodeling of the Adherens Junctions (AJs) (Abreu-Blanco et al, 2012; Carvalho et al, 2014; Hunter et al, 2015; Matsubayashi et al, 2015). After wounding, the AJ protein E-cadherin (E-cad) is downregulated at the cell boundaries facing the wound, remaining only at the lateral junctions of leading-edge cells.…”

Section: Resultsmentioning

confidence: 99%

Drp1-mediated mitochondrial fission regulates calcium and F-actin dynamics during wound healing

Ponte

Carvalho

Gagliardi

et al. 2019

Preprint

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Mitochondria adapt to cellular needs by changes in morphology through fusion and fission events, referred to as mitochondrial dynamics. Mitochondrial function and morphology are intimately connected and the dysregulation of mitochondrial dynamics is linked to several human diseases. In this work, we investigated the role of mitochondrial dynamics in wound healing in the Drosophila embryonic epidermis. Mutants for mitochondrial fusion and fission proteins fail to close their wounds, indicating that the regulation of mitochondrial dynamics is required for wound healing. By live-imaging, we found that loss of function of the mitochondrial fission protein Dynamin-related protein 1 (Drp1) compromises the increase of cytosolic and mitochondrial calcium upon wounding and leads to F-actin defects at the wound edge, culminating in wound healing impairment. Our results highlight a new role for mitochondrial dynamics in the regulation of calcium and F-actin during epithelial repair.SummaryWe show that mitochondrial dynamics proteins are required for epithelial repair. In particular, Drp1 loss-of-function leads to defects in the dynamics of cytosolic and mitochondrial calcium and F-actin upon wounding.

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Section: Resultsmentioning

confidence: 99%

Drp1-mediated mitochondrial fission regulates calcium and F-actin dynamics during wound healing

Ponte

Carvalho

Gagliardi

et al. 2019

Preprint

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“…Intriguingly, Abl loss has a similar effect, and in the case of Abl its loss impairs both actin organization at the wound edge and enrichment of the cadherin-catenin complex at tricellular junctions (Zulueta-Coarasa et al, 2014). SCAR is also critical for embryonic wound healing (Matsubayashi et al, 2015). In the future it will be important to explore which cell biological events required for wound healing are regulated by Crk.…”

Section: Crk Plays Additional Roles In the Central Nervous System Andmentioning

confidence: 99%

The Crk adapter protein is essential forDrosophilaembryogenesis, where it regulates multiple actin-dependent morphogenic events

Spracklen

Thornton-Kolbe

Bonner

et al. 2019

Preprint

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Small SH2/SH3 adapter proteins regulate cell fate and behavior by mediating interactions between cell surface receptors and downstream signaling effectors in many signal transduction pathways. The Crk family has tissue-specific roles in phagocytosis, cell migration and neuronal development, and mediates oncogenic signaling in pathways like that of Abelson kinase. However, redundancy among the two mammalian family members and the position of the Drosophila gene on the fourth chromosome precluded assessment of Crk's full role in embryogenesis. We circumvented these limitations with shRNA and CRISPR technology to assess Crk's function in Drosophila morphogenesis. We found Crk is essential beginning in the first few hours of development, where it ensures accurate mitosis by regulating orchestrated dynamics of the actin cytoskeleton to keep mitotic spindles in syncytial embryos from colliding. In this role, it positively regulates levels of the Arp2/3 complex, its regulator SCAR, and F-actin in actin caps and pseudocleavage furrows. Crk loss leads to loss of nuclei and formation of multinucleate cells. We also found roles for Crk in embryonic wound healing and in axon patterning in the nervous system, where it localizes to the axons and midline glia. Thus, Crk regulates diverse events in embryogenesis that require orchestrated cytoskeletal dynamics.

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“…dl regulation is impaired during closure in Grh KD We next investigated how Grh loss-of-function impairs E-Cad dynamics during wounding and, thus, the repair process. It has been shown that, in Drosophila embryos, the downregulation and turnover of E-Cad at the AJs is required for actin polymerization and bundle formation, leading to the assembly of the contractile cable around the wound margin (Carvalho et al, 2014;Hunter et al, 2015;Matsubayashi et al, 2015). Moreover, the Toll-NF-κB signaling pathway is required for E-Cad turnover during wound closure.…”

Section: E-cad Establishes a Link Between Cell Adhesion And Cytoskeletonmentioning

confidence: 99%

“…E-Cad turnover and recycling are important in accommodating cell shape changes, as well as actomyosin flow formation and directionality (Antunes et al, 2013;Pinheiro et al, 2017;Rauzi et al, 2010). It has recently been shown in Drosophila embryos that inhibition of E-Cad turnover leads to an impairment in actin cable formation and wound closure (Carvalho et al, 2014;Hunter et al, 2015;Matsubayashi et al, 2015). However, it is still unknown how E-Cad is regulated during wound repair.…”

Section: Introductionmentioning

confidence: 99%

Novel role for Grainy head in the regulation of cytoskeletal and junctional dynamics during epithelial repair

Cristo

Carvalho

Ponte

et al. 2018

Journal of Cell Science

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Tissue repair is critical for the maintenance of epithelial integrity and permeability. Simple epithelial repair relies on a combination of collective cell movements and the action of a contractile actomyosin cable at the wound edge that together promote the fast and efficient closure of tissue discontinuities. The Grainy head family of transcription factors (Grh in flies; GRHL1-GRHL3 in mammals) are essential proteins that have been implicated both in the development and repair of epithelia. However, the genes and the molecular mechanisms that it controls remain poorly understood. Here, we show that Grh knockdown disrupts actomyosin dynamics upon injury of the pupa epithelial tissue. This leads to the formation of an ectopic actomyosin cable away from the wound edge and impaired wound closure. We also uncovered that E-Cadherin is downregulated in the Grh-depleted tissue around the wound, likely as a consequence of Dorsal (an NF-κB protein) misregulation, which also affects actomyosin cable formation. Our work highlights the importance of Grh as a stress response factor and its central role in the maintenance of epithelial characteristics necessary for tissue repair through regulating cytoskeleton and E-Cadherin dynamics.

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Endocytosis-dependent coordination of multiple actin regulators is required for wound healing

Abstract: Live imaging of epidermal wound closure in Drosophila embryos reveals that assembly of motile F-actin at wound edges requires the endocytic remodeling of adherens junctions and is mediated by Diaphanous, SCAR, and WASp.

Cited by 41 publications

References 64 publications

Drp1-mediated mitochondrial fission regulates calcium and F-actin dynamics during wound healing

Drp1-mediated mitochondrial fission regulates calcium and F-actin dynamics during wound healing

The Crk adapter protein is essential forDrosophilaembryogenesis, where it regulates multiple actin-dependent morphogenic events

Novel role for Grainy head in the regulation of cytoskeletal and junctional dynamics during epithelial repair

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