scholarly journals Regulation of the Actin Cytoskeleton via Rho GTPase Signalling in Dictyostelium and Mammalian Cells: A Parallel Slalom

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1592
Author(s):  
Vedrana Filić ◽  
Lucija Mijanović ◽  
Darija Putar ◽  
Antea Talajić ◽  
Helena Ćetković ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Rho Gtpases ◽  
Mammalian Cells ◽  
Large Scale ◽  
Rho Gtpase ◽  
Small Gtpases ◽  
Actin Dynamics ◽  
Cellular Motility ◽  
Binary Division ◽  
Cytoskeleton Dynamics

Both Dictyostelium amoebae and mammalian cells are endowed with an elaborate actin cytoskeleton that enables them to perform a multitude of tasks essential for survival. Although these organisms diverged more than a billion years ago, their cells share the capability of chemotactic migration, large-scale endocytosis, binary division effected by actomyosin contraction, and various types of adhesions to other cells and to the extracellular environment. The composition and dynamics of the transient actin-based structures that are engaged in these processes are also astonishingly similar in these evolutionary distant organisms. The question arises whether this remarkable resemblance in the cellular motility hardware is accompanied by a similar correspondence in matching software, the signalling networks that govern the assembly of the actin cytoskeleton. Small GTPases from the Rho family play pivotal roles in the control of the actin cytoskeleton dynamics. Indicatively, Dictyostelium matches mammals in the number of these proteins. We give an overview of the Rho signalling pathways that regulate the actin dynamics in Dictyostelium and compare them with similar signalling networks in mammals. We also provide a phylogeny of Rho GTPases in Amoebozoa, which shows a variability of the Rho inventories across different clades found also in Metazoa.

Cytokinesis arrest and redistribution of actin-cytoskeleton regulatory components in cells expressing the Rho GTPase CDC42Hs

1996 ◽  
Vol 109 (2) ◽  
pp. 367-377 ◽  
Author(s):  
H. Dutartre ◽  
J. Davoust ◽  
J.P. Gorvel ◽  
P. Chavrier
Keyword(s):  
Actin Cytoskeleton ◽  
Rho Gtpases ◽  
Mammalian Cells ◽  
Laser Scanning ◽  
Rho Gtpase ◽  
Laser Scanning Microscopy ◽  
Regulatory Subunit ◽  
Confocal Laser ◽  
Complex Architectures ◽  
Immunofluorescence Labelling

In mammalian cells, Rho GTPases control the reorganisation of the actin cytoskeleton in response to growth factors. In the cytoplasm, the polymerisation of actin filaments and their organisation into complex architectures is orchestrated by numerous proteins which act either directly, by interacting with actin, or by producing secondary messengers which serve as mediators between signal transduction pathways and the microfilament organisation. We sought to determine whether the intracellular distribution of some of these regulatory components may be controlled by the Rho GTPase CDC42Hs. With this aim, we have established HeLa-derived human cell lines in which expression of a constitutively activated mutant of CDC42Hs is inducible. Morphological analysis by immunofluorescence labelling and confocal laser scanning microscopy revealed a massive reorganisation of F-actin in cortical microspikes as well as podosome-like structures located at the ventral face of the cells. Concomitantly, the cells became giant and multinucleate indicating that cytokinesis was impaired. The actin bundling protein T-plastin, the vasodilatator-stimulated phosphoprotein (VASP), a profilin ligand, as well as the 85 kDa regulatory subunit of the phosphoinosite 3-kinase redistributed with F-actin into the CDC42Hs-induced structures.

scholarly journals Grit, a GTPase-Activating Protein for the Rho Family, Regulates Neurite Extension through Association with the TrkA Receptor and N-Shc and CrkL/Crk Adapter Molecules

2002 ◽  
Vol 22 (24) ◽  
pp. 8721-8734 ◽  
Author(s):  
Takeshi Nakamura ◽  
Misako Komiya ◽  
Kiyoaki Sone ◽  
Eiji Hirose ◽  
Noriko Gotoh ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Neuronal Cells ◽  
Small Gtpases ◽  
Actin Dynamics ◽  
Gtpase Activating Protein ◽  
Interacting Protein ◽  
High Affinity Receptor ◽  
Rho Family

ABSTRACT Neurotrophins are key regulators of the fate and shape of neuronal cells and act as guidance cues for growth cones by remodeling the actin cytoskeleton. Actin dynamics is controlled by Rho GTPases. We identified a novel Rho GTPase-activating protein (Grit) for Rho/Rac/Cdc42 small GTPases. Grit was abundant in neuronal cells and directly interacted with TrkA, a high-affinity receptor for nerve growth factor (NGF). Another pool of Grit was recruited to the activated receptor tyrosine kinase through its binding to N-Shc and CrkL/Crk, adapter molecules downstream of activated receptor tyrosine kinases. Overexpression of the TrkA-binding region of Grit inhibited NGF-induced neurite elongation. Further, we found some tendency for neurite promotion in full-length Grit-overexpressing PC12 cells upon NGF stimulation. These results suggest that Grit, a novel TrkA-interacting protein, regulates neurite outgrowth by modulating the Rho family of small GTPases.

scholarly journals Rho GTPases: molecular switches that control the organization and dynamics of the actin cytoskeleton

2000 ◽  
Vol 355 (1399) ◽  
pp. 965-970 ◽  
Author(s):  
Alan Hall ◽  
Catherine D. Nobes
Keyword(s):  
Actin Cytoskeleton ◽  
Rho Gtpases ◽  
Mammalian Cells ◽  
Fundamental Property ◽  
Small Gtpases ◽  
Membrane Receptors ◽  
Embryonic Cells ◽  
Filamentous Actin ◽  
Rho Family ◽  
Plasma Membrane Receptors

The actin cytoskeleton plays a fundamental role in all eukaryotic cells—it is a major determinant of cell morphology and polarity and the assembly and disassembly of filamentous actin structures provides a driving force for dynamic processes such as cell motility, phagocytosis, growth cone guidance and cytokinesis. The ability to reorganize actin filaments is a fundamental property of embryonic cells during development; the shape changes accompanying gastrulation and dorsal closure, for example, are dependent on the plasticity of the actin cytoskeleton, while the ability of cells or cell extensions, such as axons, to migrate within the developing embryo requires rapid and spatially organized changes to the actin cytoskeleton in response to the external environment. W ork in mammalian cells over the last decade has demonstrated the central role played by the highly conserved Rho family of small GTPases in signal transduction pathways that link plasma membrane receptors to the organization of the actin cytoskeleton.

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

2001 ◽  
Vol 114 (21) ◽  
pp. 3795-3803 ◽  
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.

scholarly journals Role of Rho GTPase Interacting Proteins in Subcellular Compartments of Podocytes

2021 ◽  
Vol 22 (7) ◽  
pp. 3656
Author(s):  
Kana Asano-Matsuda ◽  
Sajida Ibrahim ◽  
Tomoko Takano ◽  
Jun Matsuda
Keyword(s):  
Rho Gtpases ◽  
Rho Gtpase ◽  
Small Gtpases ◽  
The Body ◽  
Actin Dynamics ◽  
Future Research ◽  
Cellular Functions ◽  
Waste Products ◽  
Filtration Barrier ◽  
Subcellular Compartments

The first step of urine formation is the selective filtration of the plasma into the urinary space at the kidney structure called the glomerulus. The filtration barrier of the glomerulus allows blood cells and large proteins such as albumin to be retained while eliminating the waste products of the body. The filtration barrier consists of three layers: fenestrated endothelial cells, glomerular basement membrane, and podocytes. Podocytes are specialized epithelial cells featured by numerous, actin-based projections called foot processes. Proteins on the foot process membrane are connected to the well-organized intracellular actin network. The Rho family of small GTPases (Rho GTPases) act as intracellular molecular switches. They tightly regulate actin dynamics and subsequent diverse cellular functions such as adhesion, migration, and spreading. Previous studies using podocyte-specific transgenic or knockout animal models have established that Rho GTPases are crucial for the podocyte health and barrier function. However, little attention has been paid regarding subcellular locations where distinct Rho GTPases contribute to specific functions. In the current review, we discuss cellular events involving the prototypical Rho GTPases (RhoA, Rac1, and Cdc42) in podocytes, with particular focus on the subcellular compartments where the signaling events occur. We also provide our synthesized views of the current understanding and propose future research directions.

scholarly journals Regulation of endocytic traffic by Rho GTPases

2003 ◽  
Vol 371 (2) ◽  
pp. 233-241 ◽  
Author(s):  
Britta QUALMANN ◽  
Harry MELLOR
Keyword(s):  
Actin Cytoskeleton ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Small Gtpases ◽  
Endocytic Pathway ◽  
Current Understanding ◽  
Endocytic Traffic

The members of the Rho subfamily of small GTPases are key regulators of the actin cytoskeleton. However, recent studies have provided evidence for multiple additional roles for these signalling proteins in controlling endocytic traffic. Here we review our current understanding of Rho GTPase action within the endocytic pathway and examine the potential points of convergence with the more established, actin-based functions of these signalling proteins.

scholarly journals Bacterial Guanine Nucleotide Exchange Factors SopE-Like and WxxxE Effectors

2010 ◽  
Vol 78 (4) ◽  
pp. 1417-1425 ◽  
Author(s):  
Richard Bulgin ◽  
Benoit Raymond ◽  
James A. Garnett ◽  
Gad Frankel ◽  
Valerie F. Crepin ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Rho Gtpases ◽  
Shigella Flexneri ◽  
Small Gtpases ◽  
Effector Proteins ◽  
Actin Dynamics ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
T3ss Effector

ABSTRACT Subversion of Rho family small GTPases, which control actin dynamics, is a common infection strategy used by bacterial pathogens. In particular, Salmonella enterica serovar Typhimurium, Shigella flexneri, enteropathogenic Escherichia coli (EPEC), and enterohemorrhagic Escherichia coli (EHEC) translocate type III secretion system (T3SS) effector proteins to modulate the Rho GTPases RhoA, Cdc42, and Rac1, which trigger formation of stress fibers, filopodia, and lamellipodia/ruffles, respectively. The Salmonella effector SopE is a guanine nucleotide exchange factor (GEF) that activates Rac1 and Cdc42, which induce “the trigger mechanism of cell entry.” Based on a conserved Trp-xxx-Glu motif, the T3SS effector proteins IpgB1 and IpgB2 of Shigella, SifA and SifB of Salmonella, and Map of EPEC and EHEC were grouped together into a WxxxE family; recent studies identified the T3SS EPEC and EHEC effectors EspM and EspT as new family members. Recent structural and functional studies have shown that representatives of the WxxxE effectors share with SopE a 3-D fold and GEF activity. In this minireview, we summarize contemporary findings related to the SopE and WxxxE GEFs in the context of their role in subverting general host cell signaling pathways and infection.

scholarly journals Polarized Distribution of IQGAP Proteins in Gastric Parietal Cells and Their Roles in Regulated Epithelial Cell Secretion

2003 ◽  
Vol 14 (3) ◽  
pp. 1097-1108 ◽  
Author(s):  
Rihong Zhou ◽  
Zhen Guo ◽  
Charles Watson ◽  
Emily Chen ◽  
Rong Kong ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Actin Cytoskeleton ◽  
Acid Secretion ◽  
Rho Gtpase ◽  
Apical Membrane ◽  
Basolateral Membrane ◽  
Parietal Cells ◽  
Actin Dynamics ◽  
Cell Secretion ◽  
Gastric Parietal Cells

Actin cytoskeleton plays an important role in the establishment of epithelial cell polarity. Cdc42, a member of Rho GTPase family, modulates actin dynamics via its regulators, such as IQGAP proteins. Gastric parietal cells are polarized epithelial cells in which regulated acid secretion occurs in the apical membrane upon stimulation. We have previously shown that actin isoforms are polarized to different membrane domains and that the integrity of the actin cytoskeleton is essential for acid secretion. Herein, we show that Cdc42 is preferentially distributed to the apical membrane of gastric parietal cells. In addition, we revealed that two Cdc42 regulators, IQGAP1 and IQGAP2, are present in gastric parietal cells. Interestingly, IQGAP2 is polarized to the apical membrane of the parietal cells, whereas IQGAP1 is mainly distributed to the basolateral membrane. An IQGAP peptide that competes with full-length IQGAP proteins for Cdc42-binding in vitro also inhibits acid secretion in streptolysin-O-permeabilized gastric glands. Furthermore, this peptide disrupts the association of IQGAP and Cdc42 with the apical actin cytoskeleton and prevents the apical membrane remodeling upon stimulation. We propose that IQGAP2 forms a link that associates Cdc42 with the apical cytoskeleton and thus allows for activation of polarized secretion in gastric parietal cells.

The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration

2017 ◽  
Vol 352 (2) ◽  
pp. 255-264 ◽  
Author(s):  
Magdalena Blom ◽  
Katarina Reis ◽  
Johan Heldin ◽  
Johan Kreuger ◽  
Pontus Aspenström
Keyword(s):  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Rho Gtpase ◽  
Directed Cell Migration ◽  
Cytoskeleton Dynamics

scholarly journals Regulation of Rho GTPases in the Vasculature by Cullin3-Based E3 Ligase Complexes

2021 ◽  
Vol 9 ◽  
Author(s):  
Fabienne Podieh ◽  
Peter L. Hordijk
Keyword(s):  
Rho Gtpases ◽  
Vascular Function ◽  
Rho Gtpase ◽  
Current Knowledge ◽  
E3 Ligase ◽  
Small Gtpases ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Ubiquitin E3 Ligase ◽  
Cytoskeletal Dynamics

Cullin3-based ubiquitin E3 ligases induce ubiquitination of substrates leading to their proteasomal or lysosomal degradation. BTB proteins serve as adaptors by binding to Cullin3 and recruiting substrate proteins, which enables specific recognition of a broad spectrum of targets. Hence, Cullin3 and its adaptors are involved in myriad cellular processes and organ functions. Cullin3-based ubiquitin E3 ligase complexes target small GTPases of the Rho subfamily, which are key regulators of cytoskeletal dynamics and cell adhesion. In this mini review, we discuss recent insights in Cullin3-mediated regulation of Rho GTPases and their impact on cellular function and disease. Intriguingly, upstream regulators of Rho GTPases are targeted by Cullin3 complexes as well. Thus, Rho GTPase signaling is regulated by Cullin3 on multiple levels. In addition, we address current knowledge of Cullin3 in regulating vascular function, focusing on its prominent role in endothelial barrier function, angiogenesis and the regulation of blood pressure.

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