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Septins guide noncentrosomal microtubules to promote focal adhesion disassembly in migrating cells

Daniel Merenich1, Konstantinos Nakos2, Taylor Pompan1

  • 1Department of Biological Sciences, University of the Sciences in Philadelphia, Philadelphia, PA 19104.

Molecular Biology of the Cell
|March 11, 2022
PubMed

Insights

Rac1-induced septin filaments guide noncentrosomal microtubules to focal adhesions, regulating their turnover and promoting endothelial cell migration crucial for angiogenesis and metastasis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biophysics

Background:

  • Endothelial cell migration is vital for angiogenesis and tumor metastasis.
  • Focal adhesion (FA) dynamics, involving actin and microtubules (MT), are crucial for cell migration.
  • Noncentrosomal (NC) MTs influence FA dynamics and cell polarity, but their targeting mechanism to FAs remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which noncentrosomal microtubules target focal adhesions.
  • To understand the role of septin filaments in regulating MT dynamics at FAs.
  • To investigate how MT dynamics at FAs control cell migration.

Main Methods:

  • Rac1 activation assays
  • Septin filament assembly analysis
  • Microtubule dynamics tracking at focal adhesions
  • Immunofluorescence microscopy
  • Western blotting

Main Results:

  • Rac1 induces septin filament assembly near FAs, promoting NC MT growth into FAs.
  • Septin filaments inhibit mitotic centromere-associated kinesin (MCAK)-mediated MT disassembly at FA-proximal MTs.
  • This stabilization is associated with Aurora-A kinase and cytoplasmic linker-associated protein (CLASP) recruitment.
  • Regulated MT assembly/disassembly at FAs controls FA turnover and cell migration.

Conclusions:

  • Septin filaments act as scaffolds, directing NC MTs to FAs.
  • This interaction regulates MT dynamics, crucial for FA turnover and endothelial cell migration.
  • The findings reveal a novel mechanism controlling cell migration relevant to angiogenesis and metastasis.

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