The cytoskeletal protein vinculin is acylated by myristic acid

Kellie, Stuart; Wigglesworth, Noel M.

doi:10.1016/0014-5793(87)81536-3

Cited by 42 publications

(19 citation statements)

References 27 publications

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“…In actin, arginylation changes the interaction dynamics with several binding partners and alters the polymerization properties of the proteins (Karakozova et al, 2006;Saha et al, 2010). Modification of proteins with fatty acid or prenyl residues assists localization to cellular structures and is found on cytoskeletal and adhesion proteins, such as vinculin or several members of the formin family (Han et al, 2009;Harris et al, 2010;Kellie and Wigglesworth, 1987;Resh, 2006). Nucleocytoplasmic O-GlcNAcylation (i.e.…”

Section: Other Post-translational Modificationsmentioning

confidence: 99%

Finding the weakest link – exploring integrin-mediated mechanical molecular pathways

Roca‐Cusachs

Iskratsch

Sheetz

2012

Journal of Cell Science

227

222

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SummaryFrom the extracellular matrix to the cytoskeleton, a network of molecular links connects cells to their environment. Molecules in this network transmit and detect mechanical forces, which subsequently determine cell behavior and fate. Here, we reconstruct the mechanical pathway followed by these forces. From matrix proteins to actin through integrins and adaptor proteins, we review how forces affect the lifetime of bonds and stretch or alter the conformation of proteins, and how these mechanical changes are converted into biochemical signals in mechanotransduction events. We evaluate which of the proteins in the network can participate in mechanotransduction and which are simply responsible for transmitting forces in a dynamic network. Besides their individual properties, we also analyze how the mechanical responses of a protein are determined by their serial connections from the matrix to actin, their parallel connections in integrin clusters and by the rate at which force is applied to them. All these define mechanical molecular pathways in cells, which are emerging as key regulators of cell function alongside better studied biochemical pathways.

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Section: Other Post-translational Modificationsmentioning

confidence: 99%

Finding the weakest link – exploring integrin-mediated mechanical molecular pathways

Roca‐Cusachs

Iskratsch

Sheetz

2012

Journal of Cell Science

227

222

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“…Increased labeling of membrane-bound vinculin prior to photolysis could be explained by enhanced acylation of membrane-bound vinculin. However, no difference could be detected in the specific myristoylation of cytosolic and membrane-bound vinculin [29].…”

Section: Pho Toluysis-independm T Labeling Q F Vinculinmentioning

confidence: 88%

“…4A, lanes 1 -3). [29] where about 90% of total vinculin was reported to be in the cytosol and about 10% in a crude membrane fraction. The difference may be due to the fact that these authors did not consider the nuclear fraction in their analysis.…”

Section: And Bmentioning

confidence: 99%

“…Indeed, vinculin has been reported to carry both covalently bound palmitoyl [31] and myristoyl residues [29] when immunoprecipitated from chicken embryo fibroblasts which had been incubated with the corresponding fatty acids. Some of the 3H incorporation may thcrcfore well be attributed to acylation of vinculin by the photoactivatable fatty acid.…”

Section: Pho Toluysis-independm T Labeling Q F Vinculinmentioning

confidence: 99%

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Interaction in situ of the cytoskeletal protein vinculin with bilayers studied by introducing a photoactivatable fatty acid into living chicken embryo fibroblasts

Niggli

Sommer

Brunner

et al. 1990

European Journal of Biochemistry

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The cytoskeletal protein vinculin, a putative actin -plasma-membrane linker, has been shown by hydrophobic photo-labeling to interact in vitro directly with bilayers of acidic phospholipids [Niggli et al. (1986) J. B i d . Chem. 261, 6912-69181. In order to demonstrate that such an interaction occurs also in intact cells, chicken embryo fibroblasts were incubated for 2 h with a 3H-labeled photoactivatable fatty acid, 11-(4-[3-(trifluoromethyl)diazirinyl]phenyl)-[2-"H]undecanoic acid. This resulted in biosynthetic incorporation into cellular lipids of a fraction of the fatty acid added. Following photolysis, vinculin was immunoprecipitated from different subcellular fractions using a specific polyclonal anti-vinculin antibody. The protein was recovered from both the cytosolic and the crude membrane fraction. Vinculin from both fractions incorporated label, but the membrane-associated population was at least eight times more strongly photolabeled than the cytosolic protein. Moreover, photolysis increased only labeling of the membrane-bound but not of the cytosolic protein. These results suggest that the direct interaction of vinculin with the hydrophobic core of the phospholipid layer observed in vitro may also be relevant in intact cells, and may be involved in its function as a linker protein.The widely distributed protein vinculin has been suggested to participate in actin-filament -plasma-membrane linkage. This hypothesis is mainly based on the highly specific location of vinculin in areas where this linkage occurs [l]. However, conclusive evidence confirming this hypothesis is still lacking and the molecular mechanism of the proposed linkage of vinculin to both actin filaments and the plasma membrane has not yet been clarified. Recent experiments suggest very complex interactions. Besides vinculin, the proteins talin and a-actinin are also components of areas of plasma-membraneactin attachment, such as for instance focal contacts, areas of closest contact between cultured cells and the substrate. Vinculin has been shown to interact in vitro both with talk [2] and with a-actinin [3]. Only the latter protein has conclusively been shown also to interact with actin [4]. Talin itself binds in vitro to the purified transmembrane fibronectin receptor [5]. Talin, vinculin and a-actinin may therefore constitute a chain of attachment from the plasma membrane to the actin filaments. However, such a complex has not yet been demonstrated to occur in situ. A different mechanism may be operative in adherens junctions, where only vinculin, but not talin, is present [6].Not only proteins, but also lipids may play a role in the interaction of vinculin with membranes. Vinculin has been shown to interact in vitro with acidic phospholipids [7] and, using a photoactivatable phospholipid, to insert into the hydrophobic core of liposome bilayers [8]. This insertion is critically dependent on the presence of acidic phospholipids and occurs at physiological salt and phospholipid concentrations, although it is maximal at low ionic str...

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“…Therefore we decided to examine the inhibitory activity of 6 in the presence of vinculin, a known natural substrate of Nmyristoyltransferase [39]. The relative affinity of this enzyme for 6 was determined by examining the ability of the latter to inhibit the transfer of myristic acid from [l-'4C]myristoylCoA to vinculin.…”

Section: Synthesis Of Myristoyl-carba(dethiu) -Coenzyme a 6 And Of S-mentioning

confidence: 99%

Synthesis of myristoyl‐carba(dethia)‐coenzyme A and S‐(3‐oxohexadecyl)‐coenzyme A, two potent inhibitors of myristoyl‐CoA: protein N‐myristoyltransferase

Wagner

Rétey

1991

European Journal of Biochemistry

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1. Two non-hydrolysable analogues of myristoyl-coenzyme A were synthesised and spectroscopically characterized. Myristoyl-carba(dethk)coenzyme A was prepared in a multistep synthesis starting from tridecyl vinyl ketone. S-(3-Oxohexadecyl)-coenzyme A was synthesised from 3-oxohexadecyl chloride by direct condensation with coenzyme A. In many cases, myristoylation of viral proteins is required for their association with the plasma membrane and for morphological transformation of cells [13 -151. It has also emerged that the myristoylation of retroviral gag proteins is essential for the assembly and maturation of virus particles Therefore it was of interest to determine whether nonhydrolysable fatty acyl-CoA analogues might prove to be effective inhibitors of myristoyl-CoA : protein N-myristoyltransferase which catalyses the co-translational linkage of myristoyl groups to the N-terminal glycine residues of several viral and cellular proteins.[16-181. MATERIALS AND METHODS MaterialsAcidic alumina and myristoyl chloride were from Merck (Darmstadt, FRG). ['4C]Myristoyl-CoA (54 Ci/mol) and [9,10(n)-3H]myristic acid (54 Ci/mmol, n indicates nominal position of labelling) were purchased from Amersham Buchler (Braunschweig, FRG). The octapeptide Gly-Asn-Ala-AlaCorrespondence to J. RCtey,

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The cytoskeletal protein vinculin is acylated by myristic acid

Cited by 42 publications

References 27 publications

Finding the weakest link – exploring integrin-mediated mechanical molecular pathways

Finding the weakest link – exploring integrin-mediated mechanical molecular pathways

Interaction in situ of the cytoskeletal protein vinculin with bilayers studied by introducing a photoactivatable fatty acid into living chicken embryo fibroblasts

Synthesis of myristoyl‐carba(dethia)‐coenzyme A and S‐(3‐oxohexadecyl)‐coenzyme A, two potent inhibitors of myristoyl‐CoA: protein N‐myristoyltransferase

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