Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts

  title={Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts},
  author={Clare M. Waterman-Storer and Rebecca A. Worthylake and Betty P. Liu and Keith Burridge and Edward D. Salmon},
  journal={Nature Cell Biology},
Microtubules are involved in actin-based protrusion at the leading-edge lamellipodia of migrating fibroblasts. Here we show that the growth of microtubules induced in fibroblasts by removal of the microtubule destabilizer nocodazole activates Rac1 GTPase, leading to the polymerization of actin in lamellipodial protrusions. Lamellipodial protrusions are also activated by the rapid growth of a disorganized array of very short microtubules induced by the microtubule-stabilizing drug taxol. Thus… 

The Role of Microtubule-Associated Protein 2c in the Reorganization of Microtubules and Lamellipodia during Neurite Initiation

Detailed time-lapse analyses of cultured hippocampal neurons revealed that neurites emerge from segmented lamellipodia, which then gradually extend from the cell body to become nascent growth cones, which suggests that actin- and microtubule-rich structures are reorganized in a coordinated manner.

Microtubules in cell migration.

This review summarizes the current understanding of the functions of microtubules in persistent cell migration and of the migration-associated signals that promote microtubule network polarization.

Regulation of microtubules in cell migration.

Microtubules and actin crosstalk in cell migration and division

Crosstalk between the actin cytoskeleton and microtubules promotes symmetry break to polarize cells for division, shape changes, and migration, and feedback can also occur from the cortex to alter microtubule stability.

Microtubule dynamics regulation contributes to endothelial morphogenesis

It is proposed that microtubules counter-act contractile forces of the cortical actin cytoskeleton and are required to stabilize endothelial cell protrusions in a soft three-dimensional environment.

Regulation of microtubule dynamics in 3T3 fibroblasts by Rho family GTPases.

It is concluded that Cdc42 and Rac1 have similar stimulating effects on microtubule dynamics while RhoA acts in an opposite way.

Targeting and transport: How microtubules control focal adhesion dynamics

Different aspects of the molecular mechanisms by which microtubules control FA turnover in migrating cells are beginning to emerge.

Actin-dependent lamellipodia formation and microtubule-dependent tail retraction control-directed cell migration.

It is demonstrated that the formation of lamellipodia can occur via actin polymerization independently of microtubules, but that micro Tubules are required for cell migration, tail retraction, and modulation of cell adhesion.



Positive feedback interactions between microtubule and actin dynamics during cell motility.

Actomyosin-based Retrograde Flow of Microtubules in the Lamella of Migrating Epithelial Cells Influences Microtubule Dynamic Instability and Turnover and Is Associated with Microtubule Breakage and Treadmilling

It is proposed that actomyosin-based retrograde flow of MTs causes MT breakage, forming quasi-stable noncentrosomal MTs whose turnover is regulated primarily at their minus ends.

Microtubule depolymerization induces stress fibers, focal adhesions, and DNA synthesis via the GTP-binding protein Rho.

The activation of Rho in response to microtubule depolymerization and the consequent stimulation of contractility suggest a mechanism by which microtubules may regulate microfilament function in various motile phenomena.

Microtubule-dependent control of cell shape and pseudopodial activity is inhibited by the antibody to kinesin motor domain

The results of the experiments show that many changes of phenotype induced in cells by microtubule-depolymerizing agents can be mimicked by the inhibition of motor proteins, and therefore microtubules functions in maintaining of the cell shape and polarity are mediated by motor proteins rather than by being provided by rigidity of tubulin polymer itself.

Microtubule disruption induces the formation of actin stress fibers and focal adhesions in cultured cells: possible involvement of the rho signal cascade.

It is postulate that microtubule-releasing and stress fiber-inducing factors link the intrinsically variable and irregular actin filament dynamics to coordinated and directional locomotion in the process of cell movement.

Pseudopodial activity at the active edge of migrating fibroblast is decreased after drug-induced microtubule depolymerization.

Microtubules depolymerized by colcemid, and/or intermediate filaments undergoing perinuclear collapse in the presence of this drug, are essential not only for the restriction of pseudopodial activity to one particular zone of the cell edge but also for the development of maximal activity in this zone.

Role of Actin Polymerization and Adhesion to Extracellular Matrix in Rac- and Rho-induced Cytoskeletal Reorganization

It appears, therefore, that the assembly of large integrin complexes is not required for most of the actin reorganization or cell morphology changes induced by Rac or Rho activation in Swiss 3T3 fibroblasts.

Contact formation during fibroblast locomotion: involvement of membrane ruffles and microtubules

It is proposed that all primordial contacts support traction for leading edge protrusion but that only some persist long enough to nucleate stress fiber assembly.

Taxol stabilizes microtubules in mouse fibroblast cells.

  • P. SchiffS. Horwitz
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1980
Taxol inhibited the migration behavior of fibroblast cells, but these cells did not lose their ability to produce mobile surface projections such as lamellipodia and filopodia.

Lysophosphatidic acid and microtubule-destabilizing agents stimulate fibronectin matrix assembly through Rho-dependent actin stress fiber formation and cell contraction.

It is demonstrated that Rho-dependent actin stress fiber formation and cell contraction induce increased FN binding and represent a rapid labile way that cells can modulate FN matrix assembly.