The focal-adhesion vasodilator-stimulated phosphoprotein (VASP) binds to the proline-rich domain in vinculin

Brindle, Nicholas P.J.; Holt, Mark R.; Davies, JE; Price, Caroline; Critchley, David R.

doi:10.1042/bj3180753

Cited by 191 publications

(169 citation statements)

References 32 publications

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“…Their N-terminal region, the EVH1 domain, interacts with the motif E/DFPPPPXD/E, which is present in ActA and in the cytoskeletal proteins vinculin, zyxin, palladin, and Fyb/SLAP (Brindle et al, 1996;Niebuhr et al, 1997;Carl et al, 1999;Drees et al, 2000;Krause et al, 2000;Mykkanen et al, 2001). The central domain of the Ena/VASP proteins harbors a proline-rich region that binds to profilin and, in addition, to SH3 and WW domains Gertler et al, 1996;Ermekova et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Contribution of Ena/VASP Proteins to Intracellular Motility ofListeriaRequires Phosphorylation and Proline-rich Core but Not F-Actin Binding or Multimerization

Geese

Loureiro

Bear

et al. 2002

MBoC

101

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The Listeria model system has been essential for the identification and characterization of key regulators of the actin cytoskeleton such as the Arp2/3 complex and Ena/vasodilator-stimulated phosphoprotein (VASP) proteins. Although the role of Ena/VASP proteins in Listeria motility has been extensively studied, little is known about the contributions of their domains and phosphorylation state to bacterial motility. To address these issues, we have generated a panel of Ena/ VASP mutants and, upon expression in Ena/VASP-deficient cells, evaluated their contribution to Ena/VASP function in Listeria motility. The proline-rich region, the putative G-actin binding site, and the Ser/Thr phosphorylation of Ena/VASP proteins are all required for efficient Listeria motility. Surprisingly, the interaction of Ena/VASP proteins with F-actin and their potential ability to form multimers are both dispensable for their involvement in this process. Our data suggest that Ena/VASP proteins contribute to Listeria motility by regulating both the nucleation and elongation of actin filaments at the bacterial surface.

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Section: Introductionmentioning

confidence: 99%

Contribution of Ena/VASP Proteins to Intracellular Motility ofListeriaRequires Phosphorylation and Proline-rich Core but Not F-Actin Binding or Multimerization

Geese

Loureiro

Bear

et al. 2002

MBoC

101

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“…Anchorage of microfilaments is mediated by VT that harbors two actin binding regions (11,12). Through the recruitment of the vasodilator-stimulated phosphoprotein VASP and the Arp 2/3 complex to the hinge region, vinculin is also tightly linked to actin dynamics at cell adhesion sites (13)(14)(15). Ligand interactions are regulated by an intramolecular association of VH and VT, which masks the binding sites for most ligands (12,(15)(16)(17)(18)(19).…”

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confidence: 99%

Comparative Biochemical Analysis Suggests That Vinculin and Metavinculin Cooperate in Muscular Adhesion Sites

Witt

Zieseniß

Fock

et al. 2004

Journal of Biological Chemistry

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Metavinculin, the muscle-specific splice variant of the cell adhesion protein vinculin, is characterized by a 68-amino acid insert within the C-terminal tail domain. The findings that mutations within this region correlate with hereditary idiopathic dilated cardiomyopathy in man suggest a specific contribution of metavinculin to the molecular architecture of muscular actin-membrane attachment sites, the nature of which, however, is still unknown. In mice, metavinculin is expressed in smooth and skeletal muscle, where it co-localizes with vinculin in dense plaques and costameres, respectively, but is of conspicuously low abundance in the heart. Immunoprecipitates suggest that both isoforms are present in the same complex. On the molecular level, both vinculin isoforms are regulated via an intramolecular head-tail interaction, with the metavinculin tail domain having a lower affinity for the head as compared with the vinculin tail. In addition, metavinculin displays impaired binding to acidic phospholipids and reduced homodimerization. Only in the presence of phospholipidactivated vinculin tail, the metavinculin tail domain is readily incorporated into heterodimers. Mutational analysis revealed that the metavinculin insert significantly alters binding of the C-terminal hairpin loop to acidic phospholipids. In summary, our data lead to a model in which unfurling of the metavinculin tail domain is impaired by the negative charges of the 68-amino acid insert, thus requiring vinculin to fully activate the metavinculin molecule. As a consequence, microfilament anchorage may be modulated at muscular adhesion sites through heterodimer formation.

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“…Each discrete vinculin domain recognizes multiple binding partners: the vinculin head (Vh) 4 binds to talin, ␣-actinin, and IpaA (14 -16); the prolinerich linker interacts with vasodilator stimulated phosphoprotein (VASP), CAP/ponsin, vinexin, and the Arp2/3 complex (17)(18)(19)(20); the vinculin tail (Vt) associates with filamentous actin (F-actin), phosphatidylinositol (4,5)-bisphosphate, and paxillin (21)(22)(23). In the autoinhibitory form of vinculin, tight intramolecular interactions between Vh and Vt occlude binding to most of its ligands (13).…”

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confidence: 99%

The Vinculin C-terminal Hairpin Mediates F-actin Bundle Formation, Focal Adhesion, and Cell Mechanical Properties

Shen

Tolbert

Guilluy

et al. 2011

Journal of Biological Chemistry

112

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Vinculin is an essential and highly conserved cell adhesion protein, found at both focal adhesions and adherens junctions, where it couples integrins or cadherins to the actin cytoskeleton. Vinculin is involved in controlling cell shape, motility, and cell survival, and has more recently been shown to play a role in force transduction. The tail domain of vinculin (Vt) contains determinants necessary for binding and bundling of actin filaments. Actin binding to Vt has been proposed to induce formation of a Vt dimer that is necessary for cross-linking actin filaments. Results from this study provide additional support for actininduced Vt self-association. Moreover, the actin-induced Vt dimer appears distinct from the dimer formed in the absence of actin. To better characterize the role of the Vt strap and carboxyl terminus (CT) in actin binding, Vt self-association, and actin bundling, we employed smaller amino-terminal (NT) and CT deletions that do not perturb the structural integrity of Vt. Although both NT and CT deletions retain actin binding, removal of the CT hairpin (1061-1066) selectively impairs actin bundling in vitro. Moreover, expression of vinculin lacking the CT hairpin in vinculin knock-out murine embryonic fibroblasts affects the number of focal adhesions formed, cell spreading as well as cellular stiffening in response to mechanical force.The ability of cells to sense and respond to environmental cues such as mechanical forces is critical for multiple cellular processes including embryogenesis and wound healing (1-3). To transmit forces across the cell membrane in both directions, the actin cytoskeleton couples transmembrane receptors (integrin or cadherin), through points of cell adhesion consisting of multiple protein complexes that form cell-extracellular matrix (focal adhesions) and cell-cell (adherens junctions) contacts (3, 4). Vinculin is an abundant protein found in both focal adhesions and adherens junctions, and plays a key role in regulating cell morphology, cell motility, and force transduction (2, 5). Vinculin is essential during development as vinculin knockout (KO) mouse embryos fail to survive beyond day E10 with extensive defects in myocardial and endocardial structures (6). Consistent with a role in muscle structure, vinculin KO mice are predisposed to stress-induced cardiomyopathy (7). Moreover, mutations and deletions in the tail domain of metavinculin, a splice isoform of vinculin, are associated with dilated cardiomyopathy (8 -10). Vinculin also possesses tumor suppressor properties as vinculin KO cells are less adherent, have a rounded morphology, reduced lamellipodial stability, increased motility (6, 11), and are resistant to apoptosis and anoikis (12).Vinculin is a highly conserved cytoskeletal protein that has 1066 residues and contains a globular head, a flexible prolinerich linker, and a tail domain (13). Each discrete vinculin domain recognizes multiple binding partners: the vinculin head (Vh) 4 binds to talin, ␣-actinin, and IpaA (14 -16); the prolinerich linker inte...

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The focal-adhesion vasodilator-stimulated phosphoprotein (VASP) binds to the proline-rich domain in vinculin

Cited by 191 publications

References 32 publications

Contribution of Ena/VASP Proteins to Intracellular Motility ofListeriaRequires Phosphorylation and Proline-rich Core but Not F-Actin Binding or Multimerization

Contribution of Ena/VASP Proteins to Intracellular Motility ofListeriaRequires Phosphorylation and Proline-rich Core but Not F-Actin Binding or Multimerization

Comparative Biochemical Analysis Suggests That Vinculin and Metavinculin Cooperate in Muscular Adhesion Sites

The Vinculin C-terminal Hairpin Mediates F-actin Bundle Formation, Focal Adhesion, and Cell Mechanical Properties

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