scholarly journals Shear stress–induced endothelial cell polarization is mediated by Rho and Rac but not Cdc42 or PI 3-kinases

2003 ◽  
Vol 161 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Beata Wojciak-Stothard ◽  
Anne J. Ridley
Keyword(s):  
Shear Stress ◽  
Cell Shape ◽  
Rho Kinase ◽  
Cell Movement ◽  
Cell Polarization ◽  
Migration Speed ◽  
Rhoa Activity ◽  
Endothelial Response ◽  
And Migration ◽  
Shape Changes

Shear stress induces endothelial polarization and migration in the direction of flow accompanied by extensive remodeling of the actin cytoskeleton. The GTPases RhoA, Rac1, and Cdc42 are known to regulate cell shape changes through effects on the cytoskeleton and cell adhesion. We show here that all three GTPases become rapidly activated by shear stress, and that each is important for different aspects of the endothelial response. RhoA was activated within 5 min after stimulation with shear stress and led to cell rounding via Rho-kinase. Subsequently, the cells respread and elongated within the direction of shear stress as RhoA activity returned to baseline and Rac1 and Cdc42 reached peak activation. Cell elongation required Rac1 and Cdc42 but not phosphatidylinositide 3-kinases. Cdc42 and PI3Ks were not required to establish shear stress–induced polarity although they contributed to optimal migration speed. Instead, Rho and Rac1 regulated directionality of cell movement. Inhibition of Rho or Rho-kinase did not affect the cell speed but significantly increased cell displacement. Our results show that endothelial cells reorient in response to shear stress by a two-step process involving Rho-induced depolarization, followed by Rho/Rac-mediated polarization and migration in the direction of flow.

FilGAP and its close relatives: a mediator of Rho–Rac antagonism that regulates cell morphology and migration

2013 ◽  
Vol 453 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Fumihiko Nakamura
Keyword(s):  
Actin Cytoskeleton ◽  
Gene Product ◽  
Rho Kinase ◽  
Leading Edge ◽  
Filamin A ◽  
Filamentous Actin ◽  
Rhoa Activity ◽  
Cell Protrusion ◽  
And Migration ◽  
Close Relatives

Cell migration, phagocytosis and cytokinesis are mechanically intensive cellular processes that are mediated by the dynamic assembly and contractility of the actin cytoskeleton. GAPs (GTPase-activating proteins) control activities of the Rho family proteins including Cdc42, Rac1 and RhoA, which are prominent upstream regulators of the actin cytoskeleton. The present review concerns a class of Rho GAPs, FilGAP (ARHGAP24 gene product) and its close relatives (ARHGAP22 and AHRGAP25 gene products). FilGAP is a GAP for Rac1 and a binding partner of FLNa (filamin A), a widely expressed F-actin (filamentous actin)-cross-linking protein that binds many different proteins that are important in cell regulation. Phosphorylation of FilGAP serine/threonine residues and binding to FLNa modulate FilGAP's GAP activity and, as a result, its ability to regulate cell protrusion and spreading. FLNa binds to FilGAP at F-actin-enriched sites, such as at the leading edge of the cell where Rac1 activity is controlled to inhibit actin assembly. FilGAP then dissociates from FLNa in actin networks by myosin-dependent mechanical deformation of FLNa's FilGAP-binding site to relocate at the plasma membrane by binding to polyphosphoinositides. Since actomyosin contraction is activated downstream of RhoA–ROCK (Rho-kinase), RhoA activity regulates Rac1 through FilGAP by signalling to the force-generating system. FilGAP and the ARHGAP22 gene product also act as mediators between RhoA and Rac1 pathways, which lead to amoeboid and mesenchymal modes of cell movements respectively. Therefore FilGAP and its close relatives are key regulators that promote the reciprocal inhibitory relationship between RhoA and Rac1 in cell shape changes and the mesenchymal–amoeboid transition in tumour cells.

scholarly journals Actin polymerization or myosin contraction: two ways to build up cortical tension for symmetry breaking

2013 ◽  
Vol 368 (1629) ◽  
pp. 20130005 ◽  
Author(s):  
Kevin Carvalho ◽  
Joël Lemière ◽  
Fahima Faqir ◽  
John Manzi ◽  
Laurent Blanchoin ◽  
...  
Keyword(s):  
Symmetry Breaking ◽  
Self Assembly ◽  
Actin Filaments ◽  
Cell Shape ◽  
Actin Polymerization ◽  
Cell Polarization ◽  
Critical Tension ◽  
Cell Shape Changes ◽  
Myosin Motors ◽  
Shape Changes

Cells use complex biochemical pathways to drive shape changes for polarization and movement. One of these pathways is the self-assembly of actin filaments and myosin motors that together produce the forces and tensions that drive cell shape changes. Whereas the role of actin and myosin motors in cell polarization is clear, the exact mechanism of how the cortex, a thin shell of actin that is underneath the plasma membrane, can drive cell shape changes is still an open question. Here, we address this issue using biomimetic systems: the actin cortex is reconstituted on liposome membranes, in an ‘outside geometry’. The actin shell is either grown from an activator of actin polymerization immobilized at the membrane by a biotin–streptavidin link, or built by simple adsorption of biotinylated actin filaments to the membrane, in the presence or absence of myosin motors. We show that tension in the actin network can be induced either by active actin polymerization on the membrane via the Arp2/3 complex or by myosin II filament pulling activity. Symmetry breaking and spontaneous polarization occur above a critical tension that opens up a crack in the actin shell. We show that this critical tension is reached by growing branched networks, nucleated by the Arp2/3 complex, in a concentration window of capping protein that limits actin filament growth and by a sufficient number of motors that pull on actin filaments. Our study provides the groundwork to understanding the physical mechanisms at work during polarization prior to cell shape modifications.

scholarly journals Rho-kinase Controls Cell Shape Changes during Cytokinesis

2006 ◽  
Vol 16 (4) ◽  
pp. 359-370 ◽  
Author(s):  
Gilles R.X. Hickson ◽  
Arnaud Echard ◽  
Patrick H. O'Farrell
Keyword(s):  
Cell Shape ◽  
Rho Kinase ◽  
Cell Shape Changes ◽  
Shape Changes

scholarly journals Role of P120 Ras-Gap in Directed Cell Movement

2000 ◽  
Vol 149 (2) ◽  
pp. 457-470 ◽  
Author(s):  
Sarang V. Kulkarni ◽  
Gerald Gish ◽  
Peter van der Geer ◽  
Mark Henkemeyer ◽  
Tony Pawson
Keyword(s):  
Cell Polarity ◽  
Cell Movement ◽  
Focal Adhesions ◽  
Cell Polarization ◽  
Actin Stress Fiber ◽  
Dependent Manner ◽  
Directional Movement ◽  
Complete Cell ◽  
And Migration

We have used cell lines deficient in p120 Ras GTPase activating protein (Ras-GAP) to investigate the roles of Ras-GAP and the associated p190 Rho-GAP (p190) in cell polarity and cell migration. Cell wounding assays showed that Ras-GAP–deficient cells were incapable of establishing complete cell polarity and migration into the wound. Stimulation of mutant cells with growth factor rescued defects in cell spreading, Golgi apparatus fragmentation, and polarized vesicular transport and partially rescued migration in a Ras-dependent manner. However, for directional movement, the turnover of stress fibers and focal adhesions to produce an elongate morphology was dependent on the constitutive association between Ras-GAP and p190, independent of Ras regulation. Disruption of the phosphotyrosine-mediated Ras-GAP/p190 complex by microinjecting synthetic peptides derived from p190 sequences in wild-type cells caused a suppression of actin filament reorientation and migration. From these observations we suggest that although Ras-GAP is not directly required for motility per se, it is important for cell polarization by regulating actin stress fiber and focal adhesion reorientation when complexed with 190. This observation suggests a specific function for Ras-GAP separate from Ras regulation in cell motility.

Patterns of Interaction Between Cytoskeletal Elements of Cultured Cells: Modification by Cytochalasin D and A Tumor Promotor

1982 ◽  
Vol 40 ◽  
pp. 8-11
Author(s):  
Manfred Schliwa
Keyword(s):  
Cell Shape ◽  
Intracellular Transport ◽  
Cultured Cells ◽  
Cell Movement ◽  
Structural Basis ◽  
Tumor Promotor ◽  
Associated Proteins ◽  
Cytoskeletal Elements ◽  
Patterns Of Interaction ◽  
Shape Changes

Immunofluorescence and electron microscopy have identified three major filament types in a wide variety of cultured cells: microtubules, intermediate filaments, and microfilaments (F-actin). The complex of these filaments and their associated proteins is now commonly referred to as the cytoskeleton and is generally believed to form the structural basis for such cellular activities as cell movement, intracellular transport, and cell shape changes.

scholarly journals Cdc42 regulates junctional actin but not cell polarization in the Caenorhabditis elegans epidermis

2017 ◽  
Vol 216 (11) ◽  
pp. 3729-3744 ◽  
Author(s):  
Yuliya Zilberman ◽  
Joshua Abrams ◽  
Dorian C. Anderson ◽  
Jeremy Nance
Keyword(s):  
Caenorhabditis Elegans ◽  
Epidermal Cell ◽  
Cell Shape ◽  
Time Lapse ◽  
Cell Polarization ◽  
Epithelial Morphogenesis ◽  
Actin Organization ◽  
Protein Levels ◽  
Guanosine Triphosphatase ◽  
Shape Changes

During morphogenesis, adherens junctions (AJs) remodel to allow changes in cell shape and position while preserving adhesion. Here, we examine the function of Rho guanosine triphosphatase CDC-42 in AJ formation and regulation during Caenorhabditis elegans embryo elongation, a process driven by asymmetric epidermal cell shape changes. cdc-42 mutant embryos arrest during elongation with epidermal ruptures. Unexpectedly, we find using time-lapse fluorescence imaging that cdc-42 is not required for epidermal cell polarization or junction assembly, but rather is needed for proper junctional actin regulation during elongation. We show that the RhoGAP PAC-1/ARHGAP21 inhibits CDC-42 activity at AJs, and loss of PAC-1 or the interacting linker protein PICC-1/CCDC85A-C blocks elongation in embryos with compromised AJ function. pac-1 embryos exhibit dynamic accumulations of junctional F-actin and an increase in AJ protein levels. Our findings identify a previously unrecognized molecular mechanism for inhibiting junctional CDC-42 to control actin organization and AJ protein levels during epithelial morphogenesis.

scholarly journals Pulsed actomyosin contractions in morphogenesis

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 142 ◽  
Author(s):  
Ann Sutherland ◽  
Alyssa Lesko
Keyword(s):  
Cell Shape ◽  
Normal Development ◽  
Tissue Growth ◽  
Model Systems ◽  
Cellular Processes ◽  
Cytoskeletal Networks ◽  
And Migration ◽  
Shape Changes

Cell and tissue shape changes are the fundamental elements of morphogenesis that drive normal development of embryos into fully functional organisms. This requires a variety of cellular processes including establishment and maintenance of polarity, tissue growth and apoptosis, and cell differentiation, rearrangement, and migration. It is widely appreciated that the cytoskeletal networks play an important role in regulating many of these processes and, in particular, that pulsed actomyosin contractions are a core cellular mechanism driving cell shape changes and cell rearrangement. In this review, we discuss the role of pulsed actomyosin contractions during developmental morphogenesis, advances in our understanding of the mechanisms regulating actomyosin pulsing, and novel techniques to probe the role of pulsed actomyosin processes in in vivo model systems.

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