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Coordination of microtubules and the actin cytoskeleton by the Rho effector mDia1

T Ishizaki1, Y Morishima, M Okamoto

  • 1Department of Pharmacology, Kyoto University Faculty of Medicine, Sakyo, Kyoto 606-8501, Japan.

Nature Cell Biology
|January 9, 2001
PubMed

Insights

The protein mDia1 coordinates microtubules and actin cytoskeleton for cell movement. Its FH2 and FH1 regions are key to this process, influencing cell shape and cytoskeletal organization.

Area of Science:

  • Cell Biology
  • Cytoskeletal Dynamics
  • Molecular Cell Biology

Background:

  • Microtubule and actin cytoskeleton coordination is crucial for cell motility.
  • mDia1, a formin-homology protein and Rho effector, plays a role in cytoskeletal organization.
  • mDia1 possesses a Rho-binding domain, FH1, and FH2 regions.

Purpose of the Study:

  • To investigate the role of mDia1 in coordinating microtubules and actin.
  • To determine the specific functions of mDia1's FH1 and FH2 regions in cell morphology and cytoskeletal organization.

Main Methods:

  • Expression of an active mDia1 mutant (mDia1(DeltaN3)) lacking the Rho-binding domain in HeLa cells.
  • Co-expression experiments with FH2-region fragments and FH2 point mutants of mDia1(DeltaN3).
  • Microscopic analysis of cell elongation, microtubule alignment, and F-actin bundle organization.

Main Results:

  • Expression of mDia1(DeltaN3) induced bipolar cell elongation and aligned microtubules parallel to F-actin bundles.
  • Co-expression of an FH2 fragment abolished mDia1(DeltaN3)-induced cell elongation and microtubule alignment.
  • FH2 region point mutations in mDia1(DeltaN3) resulted in disorganized F-actin and abrogated cell elongation and microtubule alignment.

Conclusions:

  • mDia1, through its FH2 and FH1 regions, plays a critical role in coordinating microtubules and the actin cytoskeleton.
  • The FH2 region appears essential for mDia1's function in cell elongation and microtubule alignment.
  • The FH1 region may also contribute to the coordination of F-actin bundles.

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