Nonmuscle myosin 2 regulates cortical stability during sprouting angiogenesis

Xuefei Ma, Yutaka Uchida, Tingyi Wei, Chengyu Liu, Ralf H. Adams, Yoshiaki Kubota, J. Silvio Gutkind, Yoh Suke Mukouyama, Robert S. Adelstein

Research output: Contribution to journalArticle

Abstract

Among the three nonmuscle myosin 2 (NM2) paralogs, NM 2A and 2B, but not 2C, are detected in endothelial cells. To study the role of NM2 in vascular formation, we ablate NM2 in endothelial cells in mice. Ablating NM2A, but not NM2B, results in reduced blood vessel coverage and increased vascular branching in the developing mouse skin and coronary vasculature. NM2B becomes essential for vascular formation when NM2A expression is limited. Mice ablated for NM2B and one allele of NM2A develop vascular abnormalities similar to those in NM2A ablated mice. Using the embryoid body angiogenic sprouting assay in collagen gels reveals that NM2A is required for persistent angiogenic sprouting by stabilizing the endothelial cell cortex, and thereby preventing excessive branching and ensuring persistent migration of the endothelial sprouts. Mechanistically, NM2 promotes focal adhesion formation and cortical protrusion retraction during angiogenic sprouting. Further studies demonstrate the critical role of Rho kinase-activated NM2 signaling in the regulation of angiogenic sprouting in vitro and in vivo.

Original languageEnglish
Pages (from-to)1974-1987
Number of pages14
JournalMolecular biology of the cell
Volume31
Issue number18
DOIs
Publication statusPublished - 2020 Aug 15

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Ma, X., Uchida, Y., Wei, T., Liu, C., Adams, R. H., Kubota, Y., Gutkind, J. S., Mukouyama, Y. S., & Adelstein, R. S. (2020). Nonmuscle myosin 2 regulates cortical stability during sprouting angiogenesis. Molecular biology of the cell, 31(18), 1974-1987. https://doi.org/10.1091/mbc.E20-03-0175