The Actin Cytoskeleton in Cell Motility, Cancer, and Infection

The function of the highly homologous Rac1A, Rac1B, and Rac1C GTPases of the Dictyostelium Rac1 group was investigated. All three GTPases bound with an equal capacity to the IQGAP-related protein DGAP1, with a preference for the activated GTP-bound form. Strong overexpression of wild-type Rac1 GTPases N-terminally tagged with green fluorescent protein (GFP), predominantly induced the formation of numerous long filopodia. Remarkably, expression of the constitutively-activated GTPases resulted in dominant-negative phenotypes: these Rac1-V12 mutants completely lacked filopodia but formed numerous crown shaped structures resembling macropinosomes. Moreover, these mutants were severely impaired in cell motility, colony growth, phagocytosis, pinocytosis, cytokinesis and development. Transformants expressing constitutively-inactivated Rac1-N17 proteins were similar to wild-type cells, but displayed abundant and short filopodia and exhibited a moderate defect in cytokinesis. Taken together, our results indicate that the three GTPases play an identical role in signaling pathways and are key regulators of cellular activities that depend on the re-organization of the actin cytoskeleton in Dictyostelium.

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Cell motility: can Rho GTPases and microtubules point the way?

Journal of Cell Science ◽

10.1242/jcs.114.21.3795 ◽

2001 ◽

Vol 114 (21) ◽

pp. 3795-3803 ◽

Cited By ~ 2

Author(s):

Torsten Wittmann ◽

Clare M. Waterman-Storer

Keyword(s):

Actin Cytoskeleton ◽

Cell Motility ◽

Rho Gtpases ◽

Molecular Mechanisms ◽

Rho Gtpase ◽

Cell Types ◽

Small Gtpases ◽

Cell Polarization ◽

Microtubule Cytoskeleton ◽

Filament Bundles

Migrating cells display a characteristic polarization of the actin cytoskeleton. Actin filaments polymerise in the protruding front of the cell whereas actin filament bundles contract in the cell body, which results in retraction of the cell’s rear. The dynamic organization of the actin cytoskeleton provides the force for cell motility and is regulated by small GTPases of the Rho family, in particular Rac1, RhoA and Cdc42. Although the microtubule cytoskeleton is also polarized in a migrating cell, and microtubules are essential for the directed migration of many cell types, their role in cell motility is not well understood at a molecular level. Here, we discuss the potential molecular mechanisms for interplay of microtubules, actin and Rho GTPase signalling in cell polarization and motility. Recent evidence suggests that microtubules locally modulate the activity of Rho GTPases and, conversely, Rho GTPases might be responsible for the initial polarization of the microtubule cytoskeleton. Thus, microtubules might be part of a positive feedback mechanism that maintains the stable polarization of a directionally migrating cell.

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Prolactin promotes T47D cell motility through actin cytoskeleton

Maturitas ◽

10.1016/j.maturitas.2015.02.270 ◽

2015 ◽

Vol 81 (1) ◽

pp. 192

Author(s):

Vinicius Cestari do Amaral ◽

Priscilla L. da Silva ◽

Tommaso Simoncini

Keyword(s):

Actin Cytoskeleton ◽

Cell Motility ◽

T47d Cell

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