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.

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 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 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.

scholarly journals ARHGAP25, a novel Rac GTPase-activating protein, regulates phagocytosis in human neutrophilic granulocytes

Blood ◽  
2012 ◽  
Vol 119 (2) ◽  
pp. 573-582 ◽  
Author(s):  
Roland Csépányi-Kömi ◽  
Gábor Sirokmány ◽  
Miklós Geiszt ◽  
Erzsébet Ligeti
Keyword(s):  
Actin Cytoskeleton ◽  
Rho Gtpases ◽  
Active Form ◽  
Cell Types ◽  
Small Gtpases ◽  
Negative Regulator ◽  
Phagocytic Cells ◽  
Rac Gtpase

Members of the Rac/Rho family of small GTPases play an essential role in phagocytic cells in organization of the actin cytoskeleton and production of toxic oxygen compounds. GTPase-activating proteins (GAPs) decrease the amount of the GTP-bound active form of small GTPases, and contribute to the control of biologic signals. The number of potential Rac/RhoGAPs largely exceeds the number of Rac/Rho GTPases and the expression profile, and their specific role in different cell types is largely unknown. In this study, we report for the first time the properties of full-length ARHGAP25 protein, and show that it is specifically expressed in hematopoietic cells, and acts as a RacGAP both in vitro and in vivo. By silencing and overexpressing the protein in neutrophil model cell lines (PLB-985 and CosPhoxFcγR, respectively) and in primary macrophages, we demonstrate that ARHGAP25 is a negative regulator of phagocytosis acting probably via modulation of the actin cytoskeleton.

WAVE signalling: from biochemistry to biology

2006 ◽  
Vol 34 (1) ◽  
pp. 73-76 ◽  
Author(s):  
S.H. Soderling ◽  
J.D. Scott
Keyword(s):  
Cell Division ◽  
Actin Cytoskeleton ◽  
Rho Gtpase ◽  
Current Knowledge ◽  
Biological Significance ◽  
Molecular Switches ◽  
Small Gtpases ◽  
Present Review ◽  
Cellular Targets ◽  
Syndrome Protein

The small GTPases Rho, Rac and Cdc42 (cell-division cycle 42) function as molecular switches to modulate the actin cytoskeleton. They achieve this by modulating the activity of downstream cellular targets. One group of Rho GTPase effectors, WAVE (Wiskott–Aldrich syndrome protein verprolin homologous)-1, WAVE-2 and WAVE-3, function as scaffolds for actin-based signalling complexes. The present review highlights current knowledge regarding the biochemistry of the WAVE signalling complexes and their biological significance.

Rho GTPase signaling modulates cell shape and contractile phenotype in an isoactin-specific manner

2003 ◽  
Vol 285 (5) ◽  
pp. C1116-C1121 ◽  
Author(s):  
Alexey Y. Kolyada ◽  
Kathleen N. Riley ◽  
Ira M. Herman
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Actin Cytoskeleton ◽  
Cell Size ◽  
Rho Gtpase ◽  
Small Gtpases ◽  
Protein Isoforms ◽  
Stress Fibers ◽  
Contractile Phenotype ◽  
Specific Manner

Rho family small GTPases (Rho, Rac, and Cdc42) play an important role in cell motility, adhesion, and cell division by signaling reorganization of the actin cytoskeleton. Here, we report an isoactin-specific, Rho GTPase-dependent signaling cascade in cells simultaneously expressing smooth muscle and nonmuscle actin isoforms. We transfected primary cultures of microvascular pericytes, cells related to vascular smooth muscle cells, with various Rho-related and Rho-specific expression plasmids. Overexpression of dominant positive Rho resulted in the formation of nonmuscle actin-containing stress fibers. At the same time, α-vascular smooth muscle actin (αVSMactin) containing stress fibers were disassembled, resulting in a dramatic reduction in cell size. Rho activation also yielded a disassembly of smooth muscle myosin and nonmuscle myosin from stress fibers. Overexpression of wild-type Rho had similar but less dramatic effects. In contrast, dominant negative Rho and C3 exotransferase or dominant positive Rac and Cdc42 expression failed to alter the actin cytoskeleton in an isoform-specific manner. The loss of smooth muscle contractile protein isoforms in pericyte stress fibers, together with a concomitant decrease in cell size, suggests that Rho activation influences “contractile” phenotype in an isoactin-specific manner. This, in turn, should yield significant alteration in microvascular remodeling during developmental and pathologic angiogenesis.

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 Multiple Sequence Elements Facilitate Chp Rho GTPase Subcellular Location, Membrane Association, and Transforming Activity

2006 ◽  
Vol 17 (7) ◽  
pp. 3108-3121 ◽  
Author(s):  
Emily J. Chenette ◽  
Natalia Y. Mitin ◽  
Channing J. Der
Keyword(s):  
Amino Acids ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Subcellular Location ◽  
Small Gtpases ◽  
Membrane Association ◽  
Basic Amino Acids ◽  
Sequence Elements ◽  
Transforming Activity ◽  
Carboxy Terminal

Cdc42 homologous protein (Chp) is a member of the Rho family of small GTPases and shares significant sequence and functional similarity with Cdc42. However, unlike classical Rho GTPases, we recently found that Chp depends on palmitoylation, rather than prenylation, for association with cellular membranes. Because palmitoylation alone is typically not sufficient to promote membrane association, we evaluated the possibility that other carboxy-terminal residues facilitate Chp subcellular association with membranes. We found that Chp membrane association and transforming activity was dependent on the integrity of a stretch of basic amino acids in the carboxy terminus of Chp and that the basic amino acids were not simply part of a palmitoyl acyltransferase recognition motif. We also determined that the 11 carboxy-terminal residues alone were sufficient to promote Chp plasma and endomembrane association. Interestingly, stimulation with tumor necrosis factor-α activated only endomembrane-associated Chp. Finally, we found that Chp membrane association was not disrupted by Rho guanine nucleotide dissociation inhibitory proteins, which are negative regulators of Cdc42 membrane association and biological activity. In summary, the unique carboxy-terminal sequence elements that promote Chp subcellular location and function expand the complexity of mechanisms by which the cellular functions of Rho GTPases are regulated.

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.

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