Integrin Adhesions Suppress Syncytium Formation in the Drosophila Larval Epidermis
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/149562 |
Resumo: | Funding Information: We thank members of M.J.G.’s lab for comments; Jodie Polan for confocal assistance; Guy Tanentzapf, Andreas Wodarz, and Talila Volk, for fly stocks/antibodies; the Bloomington Drosophila Stock Center, the Vienna Drosophila RNAi Center, and the Kyoto stock center for fly strains; and the Developmental Studies Hybridoma Bank for antibodies. This work was supported by a March of Dimes Basil O’Connor Award (5-FY06-588) and NIH R01 GM083031 to M.J.G., NIH R01 GM084103 to J.L.K., and European Research Council Starting Grant (2007-StG-208631) to A.J. Publisher Copyright: © 2015 Elsevier Ltd. All rights reserved. |
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Integrin Adhesions Suppress Syncytium Formation in the Drosophila Larval EpidermisNeuroscience(all)Biochemistry, Genetics and Molecular Biology(all)Agricultural and Biological Sciences(all)Funding Information: We thank members of M.J.G.’s lab for comments; Jodie Polan for confocal assistance; Guy Tanentzapf, Andreas Wodarz, and Talila Volk, for fly stocks/antibodies; the Bloomington Drosophila Stock Center, the Vienna Drosophila RNAi Center, and the Kyoto stock center for fly strains; and the Developmental Studies Hybridoma Bank for antibodies. This work was supported by a March of Dimes Basil O’Connor Award (5-FY06-588) and NIH R01 GM083031 to M.J.G., NIH R01 GM084103 to J.L.K., and European Research Council Starting Grant (2007-StG-208631) to A.J. Publisher Copyright: © 2015 Elsevier Ltd. All rights reserved.Integrins are critical for barrier epithelial architecture. Integrin loss in vertebrate skin leads to blistering and wound healing defects. However, how integrins and associated proteins maintain the regular morphology of epithelia is not well understood. We found that targeted knockdown of the integrin focal adhesion (FA) complex components β-integrin, PINCH, and integrin-linked kinase (ILK) caused formation of multinucleate epidermal cells within the Drosophila larval epidermis. This phenotype was specific to the integrin FA complex and not due to secondary effects on polarity or junctional structures. The multinucleate cells resembled the syncytia caused by physical wounding. Live imaging of wound-induced syncytium formation in the pupal epidermis suggested direct membrane breakdown leading to cell-cell fusion and consequent mixing of cytoplasmic contents. Activation of Jun N-terminal kinase (JNK) signaling, which occurs upon wounding, also correlated with syncytium formation induced by PINCH knockdown. Further, ectopic JNK activation directly caused epidermal syncytium formation. No mode of syncytium formation, including that induced by wounding, genetic loss of FA proteins, or local JNK hyperactivation, involved misregulation of mitosis or apoptosis. Finally, the mechanism of epidermal syncytium formation following JNK hyperactivation and wounding appeared to be direct disassembly of FA complexes. In conclusion, the loss-of-function phenotype of integrin FA components in the larval epidermis resembles a wound. Integrin FA loss in mouse and human skin also causes a wound-like appearance. Our results reveal a novel and unexpected role for proper integrin-based adhesion in suppressing larval epidermal cell-cell fusion - a role that may be conserved in other epithelia.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNWang, YanAntunes, MarcoAnderson, Aimee E.Kadrmas, Julie L.Jacinto, AntonioGalko, Michael J.2023-02-22T22:19:58Z2015-08-312015-08-31T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article13application/pdfhttp://hdl.handle.net/10362/149562eng0960-9822PURE: 48423634https://doi.org/10.1016/j.cub.2015.07.031info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:31:25Zoai:run.unl.pt:10362/149562Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:53:46.727656Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Integrin Adhesions Suppress Syncytium Formation in the Drosophila Larval Epidermis |
title |
Integrin Adhesions Suppress Syncytium Formation in the Drosophila Larval Epidermis |
spellingShingle |
Integrin Adhesions Suppress Syncytium Formation in the Drosophila Larval Epidermis Wang, Yan Neuroscience(all) Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) |
title_short |
Integrin Adhesions Suppress Syncytium Formation in the Drosophila Larval Epidermis |
title_full |
Integrin Adhesions Suppress Syncytium Formation in the Drosophila Larval Epidermis |
title_fullStr |
Integrin Adhesions Suppress Syncytium Formation in the Drosophila Larval Epidermis |
title_full_unstemmed |
Integrin Adhesions Suppress Syncytium Formation in the Drosophila Larval Epidermis |
title_sort |
Integrin Adhesions Suppress Syncytium Formation in the Drosophila Larval Epidermis |
author |
Wang, Yan |
author_facet |
Wang, Yan Antunes, Marco Anderson, Aimee E. Kadrmas, Julie L. Jacinto, Antonio Galko, Michael J. |
author_role |
author |
author2 |
Antunes, Marco Anderson, Aimee E. Kadrmas, Julie L. Jacinto, Antonio Galko, Michael J. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Centro de Estudos de Doenças Crónicas (CEDOC) NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) RUN |
dc.contributor.author.fl_str_mv |
Wang, Yan Antunes, Marco Anderson, Aimee E. Kadrmas, Julie L. Jacinto, Antonio Galko, Michael J. |
dc.subject.por.fl_str_mv |
Neuroscience(all) Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) |
topic |
Neuroscience(all) Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) |
description |
Funding Information: We thank members of M.J.G.’s lab for comments; Jodie Polan for confocal assistance; Guy Tanentzapf, Andreas Wodarz, and Talila Volk, for fly stocks/antibodies; the Bloomington Drosophila Stock Center, the Vienna Drosophila RNAi Center, and the Kyoto stock center for fly strains; and the Developmental Studies Hybridoma Bank for antibodies. This work was supported by a March of Dimes Basil O’Connor Award (5-FY06-588) and NIH R01 GM083031 to M.J.G., NIH R01 GM084103 to J.L.K., and European Research Council Starting Grant (2007-StG-208631) to A.J. Publisher Copyright: © 2015 Elsevier Ltd. All rights reserved. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-08-31 2015-08-31T00:00:00Z 2023-02-22T22:19:58Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/149562 |
url |
http://hdl.handle.net/10362/149562 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0960-9822 PURE: 48423634 https://doi.org/10.1016/j.cub.2015.07.031 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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13 application/pdf |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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