scholarly journals Signalling to actin assembly via the WASP (Wiskott-Aldrich syndrome protein)-family proteins and the Arp2/3 complex

2004 ◽  
Vol 380 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Thomas H. MILLARD ◽  
Stewart J. SHARP ◽  
Laura M. MACHESKY
Keyword(s):  
Cell Motility ◽  
Actin Filaments ◽  
Protein Family ◽  
Actin Dynamics ◽  
Actin Assembly ◽  
Wiskott Aldrich Syndrome ◽  
Recent Developments ◽  
Filament Networks ◽  
Wasp Family Proteins ◽  
Syndrome Protein

The assembly of a branched network of actin filaments provides the mechanical propulsion that drives a range of dynamic cellular processes, including cell motility. The Arp2/3 complex is a crucial component of such filament networks. Arp2/3 nucleates new actin filaments while bound to existing filaments, thus creating a branched network. In recent years, a number of proteins that activate the filament nucleation activity of Arp2/3 have been identified, most notably the WASP (Wiskott–Aldrich syndrome protein) family. WASP-family proteins activate the Arp2/3 complex, and consequently stimulate actin assembly, in response to extracellular signals. Structural studies have provided a significant refinement in our understanding of the molecular detail of how the Arp2/3 complex nucleates actin filaments. There has also been much progress towards an understanding of the complicated signalling processes that regulate WASP-family proteins. In addition, the use of gene disruption in a number of organisms has led to new insights into the specific functions of individual WASP-family members. The present review will discuss the Arp2/3 complex and its regulators, in particular the WASP-family proteins. Emphasis will be placed on recent developments in the field that have furthered our understanding of actin dynamics and cell motility.

scholarly journals WHIMP links the actin nucleation machinery to Src-family kinase signaling during protrusion and motility

2020 ◽  
Author(s):  
Shail Kabrawala ◽  
Margaret D. Zimmer ◽  
Kenneth G. Campellone
Keyword(s):  
Tyrosine Kinase ◽  
Cell Motility ◽  
X Chromosome ◽  
Membrane Protrusion ◽  
Actin Assembly ◽  
Kinase Signaling ◽  
Src Family Kinase ◽  
Direct Role ◽  
Wasp Family Proteins ◽  
Syndrome Protein

ABSTRACTCell motility is governed by cooperation between the Arp2/3 complex and nucleation factors from the Wiskott-Aldrich Syndrome Protein (WASP) family, which together assemble actin filament networks to drive membrane protrusion. Here we identify WHIMP (WAVE Homology In Membrane Protrusions) as a new member of the WASP family. The Whimp gene is encoded on the X-chromosome of multiple animals, including mice. Murine WHIMP promotes Arp2/3-dependent actin assembly, but is less potent than other nucleation factors. Nevertheless, WHIMP-mediated Arp2/3 activation enhances both plasma membrane ruffling and wound healing migration, whereas WHIMP depletion impairs protrusion and slows motility. WHIMP expression also increases Src-family kinase activity, and WHIMP-induced ruffles contain the additional nucleation factors WAVE1, WAVE2, and N-WASP, but not JMY or WASH. Perturbing the function of Src-family kinases, WAVE proteins, or Arp2/3 complex inhibits WHIMP-driven ruffling. These results suggest that WHIMP-mediated actin assembly plays a direct role in membrane protrusion, but also results in feedback control of tyrosine kinase signaling to modulate the activation of multiple WASP-family proteins.AUTHOR SUMMARYThe actin cytoskeleton is a collection of protein polymers that assemble and disassemble within cells at specific times and locations. Sophisticated cytoskeletal regulators called nucleation factors ensure that actin polymerizes when and where it is needed, and most nucleation factors are members of the Wiskott-Aldrich Syndrome Protein (WASP) family. Several of the 8 known WASP-family proteins function in cell motility, but how the different factors collaborate with one another is not well understood. In this study, we identified WHIMP, a new WASP-family member which is encoded on the X chromosome of a variety of animals. In mouse cells, WHIMP enhances cell motility by assembling actin filaments that push the cell membrane forward. Unexpectedly, WHIMP also activates tyrosine kinase enzymes, proteins that stimulate multiple WASP-family members during motility. Our results open new avenues of research into how nucleation factors cooperate during movement and how the molecular activities that underlie motility differ in distinct cell types and organisms.

scholarly journals GRB2 Links Signaling to Actin Assembly by Enhancing Interaction of Neural Wiskott-Aldrich Syndrome Protein (N-WASp) with Actin-related Protein (ARP2/3) Complex

2000 ◽  
Vol 275 (29) ◽  
pp. 21946-21952 ◽  
Author(s):  
Marie-France Carlier ◽  
Pierre Nioche ◽  
Isabelle Broutin-L'Hermite ◽  
Rajaa Boujemaa ◽  
Christophe Le Clainche ◽  
...  
Keyword(s):  
Actin Assembly ◽  
Related Protein ◽  
Wiskott Aldrich Syndrome ◽  
Syndrome Protein

scholarly journals Actin-depolymerizing Factor and Cofilin-1 Play Overlapping Roles in Promoting Rapid F-Actin Depolymerization in Mammalian Nonmuscle Cells

2005 ◽  
Vol 16 (2) ◽  
pp. 649-664 ◽  
Author(s):  
Pirta Hotulainen ◽  
Eija Paunola ◽  
Maria K. Vartiainen ◽  
Pekka Lappalainen
Keyword(s):  
Cell Motility ◽  
Actin Filament ◽  
Actin Filaments ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Actin Depolymerizing Factor ◽  
Cytoskeletal Dynamics ◽  
Nonmuscle Cells ◽  
In Cells

Actin-depolymerizing factor (ADF)/cofilins are small actin-binding proteins found in all eukaryotes. In vitro, ADF/cofilins promote actin dynamics by depolymerizing and severing actin filaments. However, whether ADF/cofilins contribute to actin dynamics in cells by disassembling “old” actin filaments or by promoting actin filament assembly through their severing activity is a matter of controversy. Analysis of mammalian ADF/cofilins is further complicated by the presence of multiple isoforms, which may contribute to actin dynamics by different mechanisms. We show that two isoforms, ADF and cofilin-1, are expressed in mouse NIH 3T3, B16F1, and Neuro 2A cells. Depleting cofilin-1 and/or ADF by siRNA leads to an accumulation of F-actin and to an increase in cell size. Cofilin-1 and ADF seem to play overlapping roles in cells, because the knockdown phenotype of either protein could be rescued by overexpression of the other one. Cofilin-1 and ADF knockdown cells also had defects in cell motility and cytokinesis, and these defects were most pronounced when both ADF and cofilin-1 were depleted. Fluorescence recovery after photobleaching analysis and studies with an actin monomer-sequestering drug, latrunculin-A, demonstrated that these phenotypes arose from diminished actin filament depolymerization rates. These data suggest that mammalian ADF and cofilin-1 promote cytoskeletal dynamics by depolymerizing actin filaments and that this activity is critical for several processes such as cytokinesis and cell motility.

scholarly journals Actin filament dynamics are dominated by rapid growth and severing activity in the Arabidopsis cortical array

2009 ◽  
Vol 184 (2) ◽  
pp. 269-280 ◽  
Author(s):  
Christopher J. Staiger ◽  
Michael B. Sheahan ◽  
Parul Khurana ◽  
Xia Wang ◽  
David W. McCurdy ◽  
...  
Keyword(s):  
Actin Filament ◽  
Actin Filaments ◽  
Stochastic Dynamics ◽  
Actin Dynamics ◽  
Epifluorescence Microscopy ◽  
Actin Assembly ◽  
Cortical Actin ◽  
Filament Dynamics ◽  
Cortical Array

Metazoan cells harness the power of actin dynamics to create cytoskeletal arrays that stimulate protrusions and drive intracellular organelle movements. In plant cells, the actin cytoskeleton is understood to participate in cell elongation; however, a detailed description and molecular mechanism(s) underpinning filament nucleation, growth, and turnover are lacking. Here, we use variable-angle epifluorescence microscopy (VAEM) to examine the organization and dynamics of the cortical cytoskeleton in growing and nongrowing epidermal cells. One population of filaments in the cortical array, which most likely represent single actin filaments, is randomly oriented and highly dynamic. These filaments grow at rates of 1.7 µm/s, but are generally short-lived. Instead of depolymerization at their ends, actin filaments are disassembled by severing activity. Remodeling of the cortical actin array also features filament buckling and straightening events. These observations indicate a mechanism inconsistent with treadmilling. Instead, cortical actin filament dynamics resemble the stochastic dynamics of an in vitro biomimetic system for actin assembly.

scholarly journals Involvement of Wiskott-Aldrich Syndrome Protein Family Verprolin-Homologous Protein (WAVE) and Rac1 in the Phagocytosis of Amyloid-β(1 – 42) in Rat Microglia

2003 ◽  
Vol 92 (2) ◽  
pp. 115-123 ◽  
Author(s):  
Yoshihisa Kitamura ◽  
Keiichi Shibagaki ◽  
Kazuyuki Takata ◽  
Daiju Tsuchiya ◽  
Takashi Taniguchi ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Protein Family ◽  
Wiskott Aldrich Syndrome ◽  
Homologous Protein ◽  
Syndrome Protein

scholarly journals Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Julia Damiano-Guercio ◽  
Laëtitia Kurzawa ◽  
Jan Mueller ◽  
Georgi Dimchev ◽  
Matthias Schaks ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Actin Filaments ◽  
Focal Adhesions ◽  
Protein Accumulation ◽  
Actin Assembly ◽  
Filament Length ◽  
Capping Protein ◽  
Network Geometry ◽  
Positive Regulators

Cell migration entails networks and bundles of actin filaments termed lamellipodia and microspikes or filopodia, respectively, as well as focal adhesions, all of which recruit Ena/VASP family members hitherto thought to antagonize efficient cell motility. However, we find these proteins to act as positive regulators of migration in different murine cell lines. CRISPR/Cas9-mediated loss of Ena/VASP proteins reduced lamellipodial actin assembly and perturbed lamellipodial architecture, as evidenced by changed network geometry as well as reduction of filament length and number that was accompanied by abnormal Arp2/3 complex and heterodimeric capping protein accumulation. Loss of Ena/VASP function also abolished the formation of microspikes normally embedded in lamellipodia, but not of filopodia capable of emanating without lamellipodia. Ena/VASP-deficiency also impaired integrin-mediated adhesion accompanied by reduced traction forces exerted through these structures. Our data thus uncover novel Ena/VASP functions of these actin polymerases that are fully consistent with their promotion of cell migration.

scholarly journals Critical Roles of Phosphorylation and Actin Binding Motifs, but Not the Central Proline-rich Region, for Ena/Vasodilator-stimulated Phosphoprotein (VASP) Function during Cell Migration

2002 ◽  
Vol 13 (7) ◽  
pp. 2533-2546 ◽  
Author(s):  
Joseph J. Loureiro ◽  
Douglas A. Rubinson ◽  
James E. Bear ◽  
Gretchen A. Baltus ◽  
Adam V. Kwiatkowski ◽  
...  
Keyword(s):  
Cell Motility ◽  
Cell Movement ◽  
Protein Family ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Binding Motif ◽  
Conserved Sequence ◽  
Cellular Processes ◽  
Sequence Elements

The Ena/vasodilator-stimulated phosphoprotein (VASP) protein family is implicated in the regulation of a number of actin-based cellular processes, including lamellipodial protrusion necessary for whole cell translocation. A growing body of evidence derived largely from in vitro biochemical experiments using purified proteins, cell-free extracts, and pathogen motility has begun to suggest various mechanistic roles for Ena/VASP proteins in the control of actin dynamics. Using complementation of phenotypes in Ena/VASP-deficient cells and overexpression in normal fibroblasts, we have assayed the function of a panel of mutants in one member of this family, Mena, by mutating highly conserved sequence elements found in this protein family. Surprisingly, deletion of sites required for binding of the actin monomer-binding protein profilin, a known ligand of Ena/VASP proteins, has no effect on the ability of Mena to regulate random cell motility. Our analysis revealed two features essential for Ena/VASP function in cell movement, cyclic nucleotide-dependent kinase phosphorylation sites and an F-actin binding motif. Interestingly, expression of the C-terminal EVH2 domain alone is sufficient to complement loss of Ena/VASP function in random cell motility.

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