Endothelial cell invasion is controlled by dactylopodia.

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  • Additional Information
    • Source:
      Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : National Academy of Sciences
    • Subject Terms:
      Endothelial Cells/*cytology ; Nonmuscle Myosin Type IIA/*genetics ; Pseudopodia/*genetics ; rac1 GTP-Binding Protein/*genetics; Actin-Related Protein 2-3 Complex/chemistry ; Actin-Related Protein 2-3 Complex/genetics ; Animals ; Cell Surface Extensions ; Endothelial Cells/metabolism ; Mice ; Neovascularization, Pathologic/genetics ; Neovascularization, Physiologic/genetics ; Nonmuscle Myosin Type IIA/chemistry ; Transcriptional Activation/genetics
    • Abstract:
      Sprouting 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.
      Competing Interests: The authors declare no competing interest.
      (Copyright © 2021 the Author(s). Published by PNAS.)
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    • Contributed Indexing:
      Keywords: actin; angiogenesis; endothelial cells; invasion; myosin
    • Accession Number:
      0 (Actin-Related Protein 2-3 Complex)
      EC 3.6.1.- (Nonmuscle Myosin Type IIA)
      EC 3.6.5.2 (rac1 GTP-Binding Protein)
    • Publication Date:
      Date Created: 20210427 Date Completed: 20211203 Latest Revision: 20211214
    • Publication Date:
      20231215
    • Accession Number:
      PMC8106348
    • Accession Number:
      10.1073/pnas.2023829118
    • Accession Number:
      33903241