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Endothelial cell invasion is controlled by dactylopodia

2021Journal article Open access
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dc.contributor.authorFigueiredo, Ana
dc.contributor.authorBarbacena, Pedro
dc.contributor.authorRusso, Ana
dc.contributor.authorVaccaro, Silvia
dc.contributor.authorRamalho, Daniela
dc.contributor.authorPena, Andreia
dc.contributor.authorLima, Aida Pires
dc.contributor.authorRua Ferreira, Rita
dc.contributor.authorFidalgo, Marta
dc.contributor.authorEl-Marjou, Fatima
dc.contributor.authorCarvalho, Yulia
dc.contributor.authorVasconcelos, Francisca
dc.contributor.authorLennon-Duménil, Ana-Maria
dc.contributor.authorVignjevic, Danijela Matic
dc.contributor.authorFranco, Claudio
dc.date.accessioned2021-04-29T13:11:19Z
dc.date.available2021-04-29T13:11:19Z
dc.date.issued2021
dc.descriptionCopyright © 2021 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).pt_PT
dc.description.abstractSprouting angiogenesis is fundamental for development and contributes to cancer, diabetic retinopathy, and cardiovascular diseases. Sprouting angiogenesis depends on the invasive properties of endothelial tip cells. However, there is very limited knowledge on how tip cells invade into tissues. Here, we show that endothelial tip cells use dactylopodia as the main cellular protrusion for invasion into nonvascular extracellular matrix. We show that dactylopodia and filopodia protrusions are balanced by myosin IIA (NMIIA) and actin-related protein 2/3 (Arp2/3) activity. Endothelial cell-autonomous ablation of NMIIA promotes excessive dactylopodia formation in detriment of filopodia. Conversely, endothelial cell-autonomous ablation of Arp2/3 prevents dactylopodia development and leads to excessive filopodia formation. We further show that NMIIA inhibits Rac1-dependent activation of Arp2/3 by regulating the maturation state of focal adhesions. Our discoveries establish a comprehensive model of how endothelial tip cells regulate its protrusive activity and will pave the way toward strategies to block invasive tip cells during sprouting angiogenesis.pt_PT
dc.description.sponsorshipC.A.F. was supported by a European Research Council starting grant (679368), the European Union H2020-TWINN-2015—Twinning (692322), the Fundação para a Ciência e a Tecnologia funding (grants IF/00412/2012, EXPL/BEX-BCM/2258/2013, PTDC/MED-PAT/31639/2017, and PTDC/BIA-CEL/32180/2017 and fellowships CEECIND/04251/2017 and CEECIND/02589/2018), and a grant from the Fondation Leducq (17CVD03).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationProc Natl Acad Sci U S A. 2021 May 4;118(18):e2023829118pt_PT
dc.identifier.doi10.1073/pnas.2023829118pt_PT
dc.identifier.eissn1091-6490
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/10451/47603
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNational Academy of Sciencespt_PT
dc.relationIF/00412/2012pt_PT
dc.relationPRINCIPLES OF AXIAL POLARITY-DRIVEN VASCULAR PATTERNING
dc.relationTowards outstanding research and training in tumour biology at IMM
dc.relationCEECIND/04251/2017pt_PT
dc.relationDeregulated Endothelial Blood Flow Response as a cause of Diabetic Retinopathy
dc.relationIdentify the mechanisms of endothelial tip cell invasive behavior in order to inhibit physiological and pathological sprouting angiogenesis
dc.relation.publisherversionhttps://www.pnas.org/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectAngiogenesispt_PT
dc.subjectEndothelial cellspt_PT
dc.subjectInvasionpt_PT
dc.subjectActinpt_PT
dc.subjectMyosinpt_PT
dc.titleEndothelial cell invasion is controlled by dactylopodiapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitlePRINCIPLES OF AXIAL POLARITY-DRIVEN VASCULAR PATTERNING
oaire.awardTitleTowards outstanding research and training in tumour biology at IMM
oaire.awardTitleDeregulated Endothelial Blood Flow Response as a cause of Diabetic Retinopathy
oaire.awardTitleIdentify the mechanisms of endothelial tip cell invasive behavior in order to inhibit physiological and pathological sprouting angiogenesis
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/679368/EU
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/692322/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/EXPL%2FBEX-BCM%2F2258%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FMED-PAT%2F31639%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIA-CEL%2F32180%2F2017/PT
oaire.citation.issue18pt_PT
oaire.citation.titleProceedings of the National Academy of Sciencespt_PT
oaire.citation.volume118pt_PT
oaire.fundingStreamH2020
oaire.fundingStreamH2020
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
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person.familyNameMartins Figueiredo Fonseca
person.familyNameBarbacena
person.familyNameRusso
person.familyNameGrou Ramalho
person.familyNameSantos de Areosa Pena
person.familyNameRodrigues da Silva Rua Ferreira
person.familyNameFidalgo
person.familyNameCarvalho
person.familyNameVasconcelos
person.familyNameFranco
person.givenNameAna Raquel
person.givenNamePedro
person.givenNameAna Alexandra
person.givenNameDaniela Maria
person.givenNameAndreia Alexandra
person.givenNameRita Joana
person.givenNameMarta
person.givenNameYulia
person.givenNameFrancisca
person.givenNameClaudio
person.identifierD-8117-2015
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project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameEuropean Commission
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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