ORGANIZATION OF FOCAL ADHESION PLAQUES IS DISRUPTED BY ACTION OF THE HIV-1 PROTEASE

2002 ◽  
Vol 26 (6) ◽  
pp. 529-539 ◽  
Author(s):  
R Shoeman
Keyword(s):  
Focal Adhesion ◽  
Adhesion Plaques ◽  
Hiv 1

HIV-1 Tat Mediated Effects on Focal Adhesion Assembly and Permeability in Brain Microvascular Endothelial Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3105-3105
Author(s):  
Shalom Avraham ◽  
Shuxian Jiang ◽  
Tae-Hee Lee ◽  
O. Prakash ◽  
Hava Karsenty Avraham
Keyword(s):  
Endothelial Cells ◽  
Focal Adhesion ◽  
Microvascular Endothelial Cells ◽  
Mutant Form ◽  
Dependent Manner ◽  
Brain Microvascular Endothelial Cells ◽  
Adhesion Sites ◽  
Permeability Changes ◽  
Microvascular Endothelial ◽  
Hiv 1

Abstract The blood-brain barrier (BBB) is a network formed mainly by brain microvascular endothelial cells. The integrity of the BBB is critical for brain function. Breakdown of the BBB is commonly seen in AIDS patients with HIV-1-associated dementia (HAD), despite the lack of productive HIV-infection of the brain endothelium. The processes by which HIV causes these pathological conditions are not well understood. Here, we characterized the molecular mechanisms by which Tat mediates its pathogenic effects in-vitro on primary human brain microvascular endothelial cells (HBMECs). Tat treatment of HBMECs stimulated cytoskeletal organization and increased focal adhesion sites as compared to control cells or cells treated with heat-inactivated Tat. Pretreatment with Tat antibodies or with the specific inhibitor SU-1498, which interferes with VEGFR-2 (Flk-1/KDR) receptor phosphorylation, blocked the ability of Tat to stimulate focal adhesion assembly and the migration of HBMECs. Focal adhesion kinase (FAK) was tyrosine-phosphorylated by Tat and found to be an important component of focal adhesion sites. Inhibition of FAK by the dominant-interfering mutant form FRNK (FAK-related non-kinase) significantly blocked HBMEC migration and disrupted focal adhesions upon Tat activation. Furthermore, HIV-Tat induced permeability changes in HBMECs in a time dependent manner. Tat also impaired BBB permeability as observed in HIV-1 Tat transgenic mice. These studies define a mechanism for HIV-1 Tat in focal adhesion complex assembly in HBMECs, via activation of FAK, leading to cytoskeletal reorganization and permeability changes.

scholarly journals A Chemo-Mechanical Model for Extracellular Matrix and Nuclear Rigidity Regulated Size of Focal Adhesion Plaques

2016 ◽  
Vol 110 (3) ◽  
pp. 622a ◽  
Author(s):  
Xuan Cao ◽  
Yuan Lin ◽  
Tristian P. Driscoll ◽  
Janusz Franco-Barraza ◽  
Edna Cukierman ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Focal Adhesion ◽  
Mechanical Model ◽  
Adhesion Plaques

scholarly journals Compliant substratum modulates vinculin expression in focal adhesion plaques in skeletal cells

2019 ◽  
Vol 11 (2) ◽  
Author(s):  
Chenchen Zhou ◽  
Qingxuan Wang ◽  
Demao Zhang ◽  
Linyi Cai ◽  
Wei Du ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Adhesion Plaques

scholarly journals Thrombospondin modulates focal adhesions in endothelial cells.

1989 ◽  
Vol 109 (3) ◽  
pp. 1309-1319 ◽  
Author(s):  
J E Murphy-Ullrich ◽  
M Höök
Keyword(s):  
Endothelial Cells ◽  
Focal Adhesion ◽  
Adhesion Formation ◽  
Focal Adhesions ◽  
Cell Spreading ◽  
Heparin Binding ◽  
Focal Adhesion Formation ◽  
Heparin Binding Domain ◽  
Adhesion Plaques ◽  
Number Of Cells

We examined the effects of thrombospondin (TSP) in the substrate adhesion of bovine aortic endothelial cells. The protein was tested both as a substrate for cell adhesion and as a modulator of the later stages of the cell adhesive process. TSP substrates supported the attachment of some BAE cells, but not cell spreading or the formation of focal adhesion plaques. In contrast, cells seeded on fibrinogen or fibronectin substrates were able to complete the adhesive process, as indicated by the formation of focal adhesion plaques. Incubation of cells in suspension with soluble TSP before or at the time of seeding onto fibronectin substrates resulted in an inhibition of focal adhesion formation. Furthermore, the addition of TSP to fully adherent cells in situ or prespread on fibronectin substrates caused a reduction in the number of cells, which were positive for focal adhesions, although there was no significant effect on cell spreading. In a dose-dependent manner, TSP reduced the number of cells with adhesion plaques to approximately 60% of control levels. The distribution of remaining adhesion plaques in TSP-treated cells was also altered: plaques were primarily limited to the periphery of cells and were not present in the central cell body, as in control cells treated with BSA. The observed effects were specific for TSP and were not observed with platelet factor 4, beta-thromboglobulin, or fibronectin. The TSP-mediated loss of adhesion plaques was neutralized by the addition of heparin, fucoidan, other heparin-binding proteins, and by a monoclonal antibody to the heparin binding domain of TSP, but not by antibodies to the core or carboxy-terminal regions of TSP. The interaction of the heparin-binding domain of TSP with cell-associated heparan sulfate appears to be an important mechanistic component for this activity of TSP. These data indicate that TSP may have a role in destabilizing cell adhesion through prevention of focal adhesion formation and by loss of preformed focal adhesions.

scholarly journals Depletion of intracellular potassium disrupts coated pits and reversibly inhibits cell polarization during fibroblast spreading.

1993 ◽  
Vol 120 (6) ◽  
pp. 1449-1459 ◽  
Author(s):  
G Altankov ◽  
F Grinnell
Keyword(s):  
Cell Adhesion ◽  
Actin Filament ◽  
Focal Adhesion ◽  
Cell Polarization ◽  
Endocytic Pathway ◽  
Stress Fibers ◽  
Coated Pits ◽  
Intracellular Potassium ◽  
Filament Bundles ◽  
Adhesion Plaques

To learn more about the possible role of the coated pits endocytic pathway in cell adhesion, we studied attachment and spreading of fibroblasts whose coated pits were disrupted by depletion of intercellular potassium. Fibroblasts incubated in suspension in potassium-free medium lost 80% of their intracellular potassium within 10 min and showed disrupted coated pits based on fluorescence staining of clathrin. Potassium-depleted cells attached and spread on fibronectin-coated substrata over the same time course (15 min-2 h) as control cells. Unlike controls, however, potassium-depleted fibroblasts attained a radial morphology with circumferentially organized actin filament bundles and were unable to make the transition to a polarized morphology with stress fibers. In the radially spread fibroblasts, fibronectin receptors and vinculin colocalized in focal adhesion sites and appeared to be membrane insertion points for circumferentially arranged actin filament bundles, but these sites were much smaller than the focal adhesion plaques in polarized cells. The effects of potassium depletion on cell adhesion were reversible. Within 1 h after switching K(+)-depleted fibroblasts to medium containing KCl, cells developed a polarized morphology with actin stress fibers inserting into focal adhesion plaques. Coated pits also reformed on the cell surface during this time. Because formation of focal adhesion plaques preceded reappearance of clathrin-coated pits at the cell margins, it seems unlikely that coated pits play a direct role in adhesion plaque assembly. Polarization of fibroblasts upon addition of KCl was inhibited by ouabain showing that intracellular potassium was required for activity. Polarization also was inhibited when potassium-depleted cells were switched to potassium-containing medium under hypertonic or acidified conditions, both of which have been shown to inhibit receptor-mediated endocytosis. Our results suggest that the coated pit endocytic pathway is not required for initial attachment, spreading, and formation of focal adhesions by fibroblasts, but may play a role in cell polarization.

scholarly journals HIV-1 envelope induces activation of caspase-3 and cleavage of focal adhesion kinase in primary human CD4+ T cells

2000 ◽  
Vol 97 (3) ◽  
pp. 1178-1183 ◽  
Author(s):  
C. Cicala ◽  
J. Arthos ◽  
A. Rubbert ◽  
S. Selig ◽  
K. Wildt ◽  
...  
Keyword(s):  
T Cells ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Cd4 T Cells ◽  
Caspase 3 ◽  
Hiv 1

scholarly journals Identification of Tyr-397 as the primary site of tyrosine phosphorylation and pp60src association in the focal adhesion kinase, pp125FAK.

1995 ◽  
Vol 15 (5) ◽  
pp. 2819-2827 ◽  
Author(s):  
B L Eide ◽  
C W Turck ◽  
J A Escobedo
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Focal Adhesion Kinase ◽  
Tyrosine Phosphorylation ◽  
Focal Adhesion ◽  
Consensus Sequence ◽  
Sh2 Domain ◽  
Protein Tyrosine ◽  
Adhesion Plaques

A number of cellular processes, such as proliferation, differentiation, and transformation, are regulated by cell-extracellular matrix interactions. Previous studies have identified a novel tyrosine kinase, the focal adhesion kinase p125FAK, as a component of cell adhesion plaques. p125FAK was identified as a 125-kDa tyrosine-phosphorylated protein in cells transformed by the v-src oncogene. p125FAK is an intracellular protein composed of three domains: a central domain with homology to protein tyrosine kinases, flanked by two noncatalytic domains of 400 amino acids which bear no significant homology to previously cloned proteins. p125FAK is believed to play an important regulatory role in cell adhesion because it localizes to cell adhesion plaques and because its phosphorylation on tyrosine residues is regulated by binding of cell surface integrins to the extracellular matrix. Recent studies have shown that Src, through its SH2 domain, stably associates with pp125FAK and that this association prevents dephosphorylation of pp125FAK in vitro by protein tyrosine phosphatases. In this report, we identify Tyr-397 as the primary in vivo and in vitro site of p125FAK tyrosine phosphorylation and association with Src. Substituting phenylalanine for tyrosine at position 397 significantly reduces p125FAK tyrosine phosphorylation and association with Src but does not abolish p125FAK kinase activity. In addition, p125FAK kinase is able to trans-phosphorylate Tyr-397 in vitro in a kinase-deficient p125FAK variant. Phosphorylation of Tyr-397 provides a site [Y(P)AEI] that fits the consensus sequence for the binding of Src.

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