Nonmuscle myosin 2 regulates cortical stability during sprouting angiogenesis

Mol Biol Cell. 2020 Aug 15;31(18):1974-1987. doi: 10.1091/mbc.E20-03-0175. Epub 2020 Jun 17.


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.

MeSH terms

  • Angiogenesis Inducing Agents
  • Animals
  • Collagen / metabolism
  • Cytoskeletal Proteins / metabolism
  • Endothelial Cells / metabolism
  • Mice
  • Mice, Knockout
  • Morphogenesis
  • Myosin Heavy Chains / metabolism
  • Myosin Type II / metabolism
  • Neovascularization, Physiologic / genetics
  • Neovascularization, Physiologic / physiology*
  • Nonmuscle Myosin Type IIA / metabolism*
  • Nonmuscle Myosin Type IIB / metabolism*
  • Signal Transduction
  • rho-Associated Kinases / metabolism


  • Angiogenesis Inducing Agents
  • Cytoskeletal Proteins
  • Myh14 protein, mouse
  • Collagen
  • rho-Associated Kinases
  • Myosin Type II
  • Nonmuscle Myosin Type IIA
  • Nonmuscle Myosin Type IIB
  • nonmuscle myosin type IIB heavy chain
  • Myosin Heavy Chains