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Related Experiment Videos

Rac regulates endothelial morphogenesis and capillary assembly.

John O Connolly1, Nandi Simpson, Lindsay Hewlett

  • 1Department of Medicine, University College London, London WC1E 6BT, United Kingdom. J.Connolly@ucl.ac.uk

Molecular Biology of the Cell
|July 23, 2002
PubMed
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The small GTPase Rac and microtubule dynamics are crucial for endothelial cells to form capillary tubes. Rac signaling integrates cytoskeletal components, promoting tube assembly and cell migration in this vital angiogenesis process.

Area of Science:

  • Cell Biology
  • Angiogenesis Research
  • Cytoskeletal Dynamics

Background:

  • Endothelial cells form capillary tubes through branching morphogenesis, a fundamental process in angiogenesis.
  • Understanding the molecular mechanisms, particularly the roles of the cytoskeleton and Rho GTPases, is key to controlling this process.

Purpose of the Study:

  • To investigate the roles of the cytoskeleton and Rho GTPases in endothelial cell capillary tube formation using an in vitro Matrigel assay.
  • To elucidate the specific contributions of actin and microtubule dynamics and Rac signaling pathway components.

Main Methods:

  • Utilized an in vitro Matrigel overlay assay with endothelial cells.
  • Manipulated actin polymerization, actin-myosin contraction, and microtubule dynamics.
  • Assessed the involvement of Rac GTPase and p21-activated kinase (PAK).

Related Experiment Videos

Main Results:

  • Matrix-induced endothelial cell changes involve protrusions and cell alignment, preceding lumen formation and network assembly.
  • Inhibition of actin polymerization/contraction impaired cell migration but not initial morphology changes.
  • Microtubule dynamics inhibition affected both initial cell shape changes and migration.
  • Rac GTPase was essential for matrix-induced morphological changes, while PAK was required for cell motility.

Conclusions:

  • Rac signaling integrates actin and microtubule cytoskeletal functions to drive capillary tube assembly.
  • Microtubules are critical for both initial endothelial cell shape modulation and subsequent migration during tube formation.
  • The findings highlight a coordinated cytoskeletal and signaling network essential for angiogenesis.