Integrin Adhesions Suppress Syncytium Formation in the Drosophila Larval Epidermis

Bibliographic Details
Main Author: Wang, Yan
Publication Date: 2015
Other Authors: Antunes, Marco, Anderson, Aimee E., Kadrmas, Julie L., Jacinto, Antonio, Galko, Michael J.
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10362/149562
Summary: 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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spelling 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:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-22T18:09:22Zoai:run.unl.pt:10362/149562Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:39:51.124222Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
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
dc.format.none.fl_str_mv 13
application/pdf
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
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instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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