MRL proteins: Leading Ena/VASP to Ras GTPases

Legg, John A.; Machesky, Laura M.

doi:10.1038/ncb1104-1015

Cited by 9 publications

(4 citation statements)

References 10 publications

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“…In contrast, an emerging family of FPPPP motif-containing MRL proteins consisting of Mig10, RIAM, and lamellipodin (also known as PREL2) located at the leading edge appears to mediate EVH1-dependent recruitment of Ena/VASP proteins to lamellipodia (Jenzora et al, 2005;Krause et al, 2004;Lafuente et al, 2004;Quinn et al, 2006). Furthermore, the presence of a number of different signaling domains places MRL proteins in an ideal position to regulate Ena/VASP-dependent actin polymerization in response to a wide variety of signaling cascades (Legg and Machesky, 2004). Lamellipodin is present at the leading edge, even in the absence of Ena/VASP proteins, suggesting that it is upstream in signaling cascades stimulating cell migration.…”

Section: Introductionmentioning

confidence: 99%

Tes, a Specific Mena Interacting Partner, Breaks the Rules for EVH1 Binding

et al. 2007

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The intracellular targeting of Ena/VASP family members is achieved via the interaction of their EVH1 domain with FPPPP sequence motifs found in a variety of cytoskeletal proteins, including lamellipodin, vinculin, and zyxin. Here we show that the LIM3 domain of Tes, which lacks the FPPPP motif, binds to the EVH1 domain of Mena, but not to those of VASP or Evl. The structure of the LIM3:EVH1 complex reveals that Tes occludes the FPPPP-binding site and competes with FPPPP-containing proteins for EVH1 binding. Structure-based gain-of-function experiments define the molecular basis for the specificity of the Tes-Mena interaction. Consistent with in vitro observations, the LIM3 domain displaces Mena, but not VASP, from the leading edge and focal adhesions. It also regulates cell migration through a Mena-dependent mechanism. Our observations identify Tes as an atypical EVH1 binding partner and a regulator specific to a single Ena/VASP family member.

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Section: Introductionmentioning

confidence: 99%

Tes, a Specific Mena Interacting Partner, Breaks the Rules for EVH1 Binding

et al. 2007

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“…Moreover, VASP is involved in the regulation of the Rac/PAK pathway (Garcı´a Arguinzonis et al 2002) and cooperates with Diaphanous (mDia) in Rho-dependent F-actin assembly (Grosse et al 2003). Recently, proteins of the Mig10/RIAM/Lamellipodin family have been identified as candidate linkages between Ena/ VASP proteins and Ras-related GTPases (Legg and Machesky 2004).…”

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confidence: 99%

VASP-dependent regulation of actin cytoskeleton rigidity, cell adhesion, and detachment

Galler

Arguinzonis

Baumgärtner

et al. 2005

Histochem Cell Biol

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Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) proteins are established regulators of actin-based motility, platelet aggregation, and growth cone guidance. However, the molecular mechanisms involved essentially remain elusive. Here we report on a novel mechanism of VASP action, namely the regulation of tensile strength, contractility, and rigidity of the actin cytoskeleton. Compared to wild-type cells fibroblasts derived from VASP-deficient mice have thicker and more stable actin stress fibres. Furthermore focal adhesions are enlarged, myosin light chain phosphorylation is increased, and the rigidity of the filament-supported plasma membrane is elevated about three- to fourfold, as is evident from atomic force microscopy. Moreover, fibronectin-coated beads adhere stronger to the surface of VASP-deficient cells. The resistance of these beads to mechanical displacement by laser tweezers is dramatically increased in an F-actin-dependent mode. Cytoskeletal stabilization coincides with slower cell adhesion and detachment, while overall adhesion is increased. Interestingly, many of these effects observed in VASP (-/-) cells are recapitulated in VASP-overexpressing cells, hinting towards a balanced stoichiometry necessary for appropriate VASP function. Taken together, our results suggest that VASP regulates surface protrusion formation and cell adhesion through modulation of the mechanical properties of the actin cytoskeleton.

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“…Concerning downstream signaling of M-Ras, lamellipodin was identified to be a novel effector of MRas (Tasaka et al 2012). Lamellipodin is a ligand for Ena/VASP, which is an actin polymerization-promoting factor (Legg and Machesky 2004). Furthermore, Sema4D/Plexin-B1 has been shown to induce inhibition of lamellipodin action and the resultant disappearance of F-actin from distal dendrites through M-Ras GAP activity, reducing dendrite outgrowth (Tasaka et al 2012).…”

Section: Plexin-bsmentioning

confidence: 98%

Semaphorin Receptors and Their Signaling

Negishi

Oinuma

2015

Semaphorins

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Semaphorins, which are a large family of secreted and membrane-bound molecules, were initially identified as neuronal axon-guidance signaling molecules but are now known as important key regulators for cell adhesion and motility in a wide range of organ systems, such as angiogenesis and immune response. The semaphorin receptors, neuropilins and plexins, are expressed in a variety of cell types, including neurons, endothelial cells, and cancer cells. Plexins are primarily receptors responsible for intracellular semaphorin signalings. Plexins possess an intrinsic GAP (glyceraldehyde-3-phosphate) activity for R-Ras subfamily GTPases, and this GAP activity is one of the crucial signals of semaphorins. In addition, plexins associate with a variety of signaling molecules, such as Rho GEFs and Rho GAP, and these associated molecules determine the characters of semaphorin signals. On the other hand, their signalings are critically modulated by their associated co-receptor molecules, including tyrosine kinase receptors. Semaphorins provide attractive and repulsive responses in a variety of cells, but associated coreceptors of plexins frequently hold the key to conversion between attraction and repulsion. In this chapter, we focus attention on the molecular signaling systems of plexins.

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MRL proteins: Leading Ena/VASP to Ras GTPases

Cited by 9 publications

References 10 publications

Tes, a Specific Mena Interacting Partner, Breaks the Rules for EVH1 Binding

Tes, a Specific Mena Interacting Partner, Breaks the Rules for EVH1 Binding

VASP-dependent regulation of actin cytoskeleton rigidity, cell adhesion, and detachment

Semaphorin Receptors and Their Signaling

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