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Vimentin organization modulates the formation of lamellipodia

Brian T Helfand1, Melissa G Mendez, S N Prasanna Murthy

  • 1Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Molecular Biology of the Cell
|February 25, 2011
PubMed

Insights

Vimentin intermediate filaments (VIF) disassemble upon Rac1 activation, preventing lamellipodia formation at the cell front. This reveals an antagonistic relationship between VIF and cell protrusion dynamics.

Area of Science:

  • Cell Biology
  • Cytoskeleton Dynamics
  • Cell Motility

Background:

  • Vimentin intermediate filaments (VIF) are crucial cytoskeletal components in fibroblasts.
  • VIF organization changes dynamically during cell migration and in response to external stimuli.
  • The precise role of VIF in regulating cell protrusion, such as lamellipodia formation, remains incompletely understood.

Purpose of the Study:

  • To investigate the relationship between vimentin organization and lamellipodia formation in migrating fibroblasts.
  • To determine the role of Rac1 signaling and vimentin phosphorylation in VIF dynamics.
  • To elucidate the functional consequences of VIF disruption on cell polarity and motility.

Main Methods:

  • Live-cell imaging of vimentin organization in response to serum stimulation or Rac1 activation.
  • Phosphorylation site analysis of vimentin (Ser-38) using specific antibodies.
  • Perturbation of VIF organization using dominant-negative mutants, RNA silencing, and vimentin mimetic peptides.
  • Assessment of cell polarity and lamellipodia formation using microscopy.

Main Results:

  • Vimentin intermediate filaments (VIF) are present in the cell rear but absent from lamellipodia in migrating fibroblasts.
  • Serum addition or Rac1 activation triggers rapid vimentin phosphorylation at Ser-38, leading to VIF disassembly at the cell periphery.
  • Disruption of VIF organization results in the formation of cell-wide lamellipodia and reduced cell motility, indicating a loss of polarity.

Conclusions:

  • Vimentin intermediate filaments (VIF) actively antagonize lamellipodia formation at the leading edge of migrating cells.
  • Rac1-mediated phosphorylation of vimentin is a key mechanism for regulating VIF dynamics and enabling cell protrusion.
  • Proper VIF organization is essential for maintaining cell polarity and directional migration.

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