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Microtubules regulate migratory polarity through Rho/ROCK signaling in T cells

Aya Takesono1, Sarah J Heasman, Beata Wojciak-Stothard

  • 1University College London, Department of Biochemistry and Molecular Biology and Ludwig Institute for Cancer Research, London, United Kingdom.

Plos One
|January 26, 2010
PubMed
Abstract

Insights

Microtubules (MTs) are crucial for T-cell migration polarity. Disrupting MTs with nocodazole impairs uropod stability, but RhoA/ROCK inhibition restores polarity and persistent migration.

Area of Science:

  • Cell Biology
  • Immunology
  • Biophysics

Background:

  • Leukocyte migration relies on polarized cell shape with a lamellipodium and uropod.
  • Microtubules (MTs) are essential for persistent migration and chemotaxis.
  • The precise role of MTs in establishing and maintaining cell polarity during migration remains unclear.

Purpose of the Study:

  • To investigate the role of microtubules in T-cell polarity during migration.
  • To elucidate the molecular mechanisms by which MTs regulate cell shape and migratory behavior.

Main Methods:

  • Disruption of microtubules using nocodazole in T cells.
  • Assessment of cell morphology, migratory persistence, and membrane blebbing.
  • Analysis of RhoA activity and the effects of RhoA/ROCK and myosin II inhibition.

Main Results:

  • Nocodazole treatment disrupts MTs, leading to unstable uropods/lamellipodia and bleb-dependent migration.
  • MT disruption does not prevent clustering of uropod proteins, indicating MTs are key for uropod stability.
  • RhoA/ROCK pathway activation by nocodazole drives blebbing; inhibiting RhoA/ROCK or myosin II restores polarity and MT stability.

Conclusions:

  • RhoA/ROCK signaling, acting via myosin II, regulates both actomyosin contractility and MT stability.
  • MT stability and RhoA/ROCK activity are critical for switching between persistent lamellipodium-based and bleb-based migration.
  • This signaling axis provides a mechanism for modulating T-cell migratory behavior and turning frequency.

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