How VASP enhances actin-based motility

Samarin, Stanislav; Roméro, Stéphane; Kocks, Christine; Didry, Dominique; Pantaloni, Dominique; Carlier, Marie‐France

doi:10.1083/jcb.200303191

Cited by 138 publications

(158 citation statements)

References 47 publications

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“…The sensitivity of bacterial movement to small changes in the apparent number of cooperative bonds N suggests a simple mechanism by which a mutation in ActA that abrogates the binding of Ena͞VASP proteins (11) slows movement and increases activation energy: Ena͞VASP proteins normally enhance the rate of actin branch dissociation from the bacterial surface (16). Abolition of binding through mutation causes loss of this activity of Ena͞VASP, increasing N to 17.6 bonds on average, proportionally increasing E a , and halving the average speed.…”

Section: Resultsmentioning

confidence: 99%

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Adhesion controls bacterial actin polymerization-based movement

Soo

Theriot²

2005

Proc. Natl. Acad. Sci. U.S.A.

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As part of its infectious life cycle, the bacterial pathogen Listeria monocytogenes propels itself through the host-cell cytoplasm by triggering the polymerization of host-cell actin near the bacterial surface, harnessing the activity of several cytoskeletal proteins used during actin-based cell crawling. To distinguish among several classes of biophysical models of actin-based bacterial movement, we used a high-throughput tracking technique to record the movement of many individual bacteria during temperature shifts. The speed of each bacterium varied strongly with temperature, closely following the Arrhenius rate law. Among bacteria, the prefactor A of the Arrhenius dependence unexpectedly varied exponentially with apparent activation energy, E a, over a wide range (8 -21 kcal͞mol), reminiscent of the ''rate compensation effect'' of classical catalytic reactions. Average E a were increased for mutant bacteria deficient in binding Ena͞VASP proteins and bacteria moving in diluted extract. These two effects were additive. The observed temperature and rate compensation effects are consistent with a class of simple kinetic models in which the bacterium advances through the thermally driven, cooperative breakage of groups of adhesive bonds on its surface. The estimated number of coupled adhesive bonds N on the bacterial surface varies between 10 and 40 bonds. In contrast to other models, this model correctly predicts an experimentally observed negative correlation between bacterial speed and actin gel density. The idea that speed depends on adhesion, rather than polymerization, suggests several alternative mechanisms by which known cytoskeletal regulatory proteins could control cellular movement.ActA ͉ Listeria ͉ motility M any types of eukaryotic cells, including immune system lymphocytes, neurons, and cancer cells, use the forces generated by polymerizing actin filament networks to change shape and to move. In the actin polymerization-based movement of intracellular bacterial pathogens such as Listeria monocytogenes, individual bacteria harness the same cytoskeletal machinery to move within the host-cell cytoplasm (1).Several classes of biophysical models have been proposed to explain the mechanism of actin polymerization-based movement. The models differ in which steps in the motility cycle are proposed to control the rate of bacterial movement.The ''tethered elastic Brownian ratchet'' model (2) proposes that a large force generated by the network of polymerizing actin filaments in the ''comet tail'' behind the bacterium continuously induces the breakage of individual adhesive bonds between the bacterium and the surrounding actin gel, pushing the bacterium forward. In this model, bacteria move at the speed at which propulsive and adhesive forces are balanced; this equilibrium velocity depends strongly on the specific properties of actin polymerization and adhesion. The related ''elastic gel '' model (3) proposes that the elastic expansion of the actin gel behind the bacterium also contributes to propulsion, ''s...

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Section: Resultsmentioning

confidence: 99%

“…We tracked mutant bacteria expressing a mutated form of ActA that fails to bind the Ena͞ VASP actin regulatory proteins (11,16), wild-type bacteria in extract diluted with physiological buffer, which decreases the actin concentration, slowing the average bacterial speed (17), and mutant bacteria in diluted extract (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

Adhesion controls bacterial actin polymerization-based movement

Soo

Theriot²

2005

Proc. Natl. Acad. Sci. U.S.A.

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“…For example, VASP, through its EVH1 domain, binds to the proline-rich motifs in the ActA protein of Listeria monocytogenes (29 -32). The binding of VASP to the ActA protein exerts several effects on actin assembly including stimulation of the Arp2/3-mediated actin nucleation and reduction of the number of filamentous actin branches (33)(34)(35)(36)(37). The consequences of VASP-mediated protein interactions are complex and often contextually (and subcellular localization) dependent.…”

Section: Discussionmentioning

confidence: 99%

Migfilin Interacts with Vasodilator-stimulated Phosphoprotein (VASP) and Regulates VASP Localization to Cell-Matrix Adhesions and Migration

Zhang

Gkretsi

et al. 2006

Journal of Biological Chemistry

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Cell migration is a complex process that is coordinately regulated by cell-matrix adhesion and actin cytoskeleton. We report here that migfilin, a recently identified component of cell-matrix adhesions, is a biphasic regulator of cell migration. Loss of migfilin impairs cell migration. Surprisingly, overexpression of migfilin also reduces cell migration. Molecularly, we have identified vasodilator-stimulated phosphoprotein (VASP) as a new migfilin-binding protein. The interaction is mediated by the VASP EVH1 domain and a single L 104 PPPPP site located within the migfilin proline-rich domain. Migfilin and VASP form a complex in both suspended and adhered cells, and in the latter, they co-localize in cell-matrix adhesions. Functionally, migfilin facilitates VASP localization to cell-matrix adhesions. Using two different approaches (VASP-binding defective migfilin mutants and small interfering RNA-mediated VASP knockdown), we show that the interaction with VASP is crucially involved in migfilin-mediated regulation of cell migration. Our results identify migfilin as an important regulator of cell migration and provide new information on the mechanism by which migfilin regulates this process.Cell migration is a tightly controlled process that is crucially involved in embryonic development, wound repair, and other physiological processes (1-4). Abnormal cell migration is an important causal factor for the pathogenesis and/or progression of a wide variety of diseases. Understanding how cells control their motility therefore is an important topic in molecular biology.Migfilin is a recently identified widely expressed focal adhesion protein that provides a link between cell-matrix adhesions and the actin cytoskeleton (5). Migfilin consists of three structurally distinct regions. The C-terminal region of migfilin is composed of three LIM domains, which mediates the interaction with Mig-2, a focal adhesion protein that is critically involved in cell-matrix adhesion and shape modulation (5, 6). The N-terminal region of migfilin interacts with filamin (5), an actin-binding protein whose deficiency or mutations cause defects in cell migration (7,8). Between the N-terminal and the C-terminal regions lies a proline-rich domain. Unlike the N-and C-terminal domains, however, neither the binding partners nor the functions of the migfilin proline-rich domain were known. Interestingly, some human cells express not only migfilin but also a splicing variant (termed as migfilin(s)) lacking the prolinerich domain (5).In this study, we have sought to identify proteins that interact with the proline-rich domain of migfilin and investigated the roles of migfilin in regulation of cell migration. Our results show that vasodilator-stimulated phosphoprotein (VASP), 2 an actin cytoskeletal regulatory protein (reviewed in Refs. 9 -11), interacts with the proline-rich domain of migfilin. Depletion of migfilin diminished VASP localization to cell-matrix adhesions and impairs cell migration. Surprisingly, overexpression of migfilin also reduces ce...

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“…VASP decreases the branching of F-actin and increases the rate of actin polymerization, leading to the formation of long nonbranched actin filaments (22,71) as those seen in filopodia. The initial signals that start this reorganization of the actin network are, however, still elusive.…”

Section: Discussionmentioning

confidence: 99%

Temporal Dissection of β1-Integrin Signaling Indicates a Role for p130Cas-Crk in Filopodia Formation

Gustavsson¹,

Yuan

Fällman

2004

Journal of Biological Chemistry

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Invasin-promoted spreading of ␤ 1 -integrin-deficient cells, transfected with the ␤ 1A -or ␤ 1B -integrin splice variants, were used to dissect early ␤ 1 -integrin signaling events. The ␤ 1B isoform, which has a different membrane-distal part of the cytoplasmic tail from ␤ 1A , is defective in signaling and function. When plated on surfaces coated with the high affinity ligand invasin, ␤ 1B -integrin-expressing cells spread by forming filopodia with distinct adhesive phosphotyrosine complexes at the tips, without signs of lamellipodia. This suggested that the ␤ 1B -integrin mediated a partial signaling sufficient for formation of filopodia but insufficient for lamellipodia formation. When screening for proteins present in the distal filopodial phosphotyrosine complexes of ␤ 1B cells, p130Cas and the filopodia proteins vasodilator-stimulated phosphoprotein and talin were found, whereas the typical focal complex proteins focal adhesion kinase, paxillin, and vinculin were not. Invasinpromoted adhesion induced complex formation of p130Cas and the adapter Crk. Moreover, Crk together with Dock180 were present at the filopodial tips of ␤ 1B -integrin-expressing cells, and there was a prominent Rac1 activation. Expression of dominant negative variants of p130Cas or CrkII blocked ␤ 1B -integrin-mediated filopodia formation, indicating that this signaling scaffold is central in this process.

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How VASP enhances actin-based motility

Cited by 138 publications

References 47 publications

Adhesion controls bacterial actin polymerization-based movement

Adhesion controls bacterial actin polymerization-based movement

Migfilin Interacts with Vasodilator-stimulated Phosphoprotein (VASP) and Regulates VASP Localization to Cell-Matrix Adhesions and Migration

Temporal Dissection of β1-Integrin Signaling Indicates a Role for p130Cas-Crk in Filopodia Formation

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