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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Focal contacts are transmembrane links between the extracellular matrix and the actin cytoskeleton that play a critical role in directed cell migration, adhesion, and normal growth. Several different component proteins of the focal contact show developmentally dependent changes in expression, suggesting that this is an important mechanism by which focal contact formation is controlled during embryogenesis. In this report we examine the expression of focal contact-associated proteins in human fetal and neonatal melanocytes using Western blotting. We show that expression of paxillin, a 69-kDa vinculin binding protein, is fourfold higher in neonatal melanocytes than in fetal melanocytes. Further, we show that talin, a high molecular weight structural protein that links integrins to the actin cytoskeleton, is proteolytically cleaved in fetal, but not in neonatal melanocytes. Immunofluorescence microscopy of cells grown on fibronectin confirmed the presence of paxillin, talin, and vinculin at the ends of actin stress fibers at presumptive focal contacts in melanocytes. Adhesion experiments to extracellular matrix ligands revealed significant differences in adhesion of fetal and neonatal melanocytes to fibronectin. The developmentally specific changes in focal contact protein expression observed suggest that this may be an important mechanism by which focal contact assembly is controlled in human melanocytes during development.
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PMID:Developmental regulation of focal contact protein expression in human melanocytes. 861 74

L-Plastin is a calcium-regulated actin bundling protein expressed in leukocytes and some transformed cells, which is phosphorylated on serine in response to several different leukocyte-activating stimuli. Adhesion to immune complexes induced L-plastin phosphorylation in neutrophils, as did phagocytosis of IgG-opsonized particles, but insoluble immune complexes in suspension were very inefficient activators of L-plastin phosphorylation. Neutrophils express two IgG Fc receptors, the transmembrane FcgammaRII and the glycan phosphoinositol-linked FcgammaRIIIB. Use of monoclonal antibodies that distinguished the two Fc receptors demonstrated that FcgammaRII ligation was 100-fold more potent at signaling L-plastin phosphorylation than occupancy of FcgammaRIIIB. Depletion of intracellular calcium did not affect FcgammaRII-activated L-plastin phosphorylation, demonstrating that any potential regulation of plastin function by calcium did not affect its phosphorylation. Adhesion to immune complexes caused L-plastin to localize to podosomes, since it colocalized with actin to discrete, punctate Triton X-100-insoluble sites on the adherent neutrophil surface in a pattern indistinguishable from vinculin and alpha-actinin. Nonetheless, localization to podosomes was not required for L-plastin phosphorylation, since both neutrophils from a patient with leukocyte adhesion deficiency (CD18 deficiency) and neutrophils treated with anti-CD18 F(ab')2, which do not form podosomes upon adhesion to immune complexes, phosphorylated L-plastin normally. Indeed, L-plastin was normally phosphorylated in response to adhesion to immune complexes even when the actin cytoskeleton was disrupted with cytochalasin D. We conclude that efficient FcgammaRII-mediated phosphorylation of L-plastin requires cell adhesion but does not require IgG-induced rearrangements of the actin cytoskeleton. These data suggest a model in which plastin phosphorylation and localization to the actin cytoskeleton can act as two distinct mechanisms regulating L-plastin functions in neutrophils adherent to immune complexes.
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PMID:FcgammaRII-mediated adhesion and phagocytosis induce L-plastin phosphorylation in human neutrophils. 866 66

Different functions have been proposed for osteocytes over time, but it is now generally accepted that their most important task lies in the sensing of strain caused by mechanical loading on bone. The fact that mechanical strain can be sensed as deformation of the extracellular matrix or as fluid shear stress along the cell, in the space between cell membrane and extracellular matrix, requires that osteocytes have close (specialized) contact with the bone matrix. We studied to which extracellular matrix proteins isolated chicken osteocytes adhere and whether this adhesion is mediated by specific cell adhesion receptors called integrins. The adhesive properties of the osteocytes were compared with that of osteoblasts. Osteocytes (and osteoblasts) adhere to the same substrates (i.e., collagen types I and II, collagen fibers, osteopontin, osteonectin, fibronectin, fibrinogen, thrombospondin, and laminin). Cell spreading varied between substrates, from all cells rounded on thrombospondin to all cells fully spread out on osteopontin, osteonectin, vitronectin, fibronectin, fibrinogen, and laminin. The percentage of osteocytes adhered was equivalent to that of osteoblasts adhered on all substrates except osteopontin and vitronectin, where osteocytes adhered less. The adhesion of osteocytes and osteoblasts to osteopontin, osteonectin, vitronectin, and fibrinogen was strongly inhibited, and to fibronectin and laminin moderately, by an RGD peptide. No RGD inhibition was found on collagen. An antibody against chicken integrin alpha v beta 3, the monoclonal antibody (MAb) 23C6, did not interfere with the adhesion of osteocytes and osteoblasts to matrix proteins, whereas an MAb against chicken integrin subunit beta 1 (CSAT) strongly inhibited adhesion to all substrates. Labeling with osteocyte-specific MAbs (OB7.3, OB37.4, and OB37.11) also did not hinder the adhesion of osteocytes to collagen type I, vitronectin, and osteopontin. Adhesion sites on osteocytes were small compared with the large adhesion plaques of osteoblasts, as demonstrated by interference reflection microscopy and immunocytochemically by staining for vinculin. Osteocyte adhesion is analogous to osteoblast adhesion with regard to the range of extracellular matrix proteins to which they adhere. The adhesion is mediated by the integrin subunit beta 1, but other integrins or nonintegrin adhesion receptors are also involved. Osteocytes make contact with the extracellular matrix via small attachment points which colocalize with vinculin. This connection between the bone matrix and the cytoskeleton may be important for osteocytic sensing of mechanical strain, as it supplies a transduction route of extracellular (mechanical) signals into intracellular messages.
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PMID:Adhesive properties of isolated chick osteocytes in vitro. 872 86

Src-homology 3 (SH3) domain is a 60-70-amino acid motif present in a large variety of signal transduction and cytoskeletal proteins. We used reverse transcriptase-polymerase chain reaction with degenerate and specific primers and chicken brain mRNA to clone a cDNA that codes for a novel SH3 domain-containing protein. The sequence predicts a 448-amino acid polypeptide with a molecular mass of 51, 971 daltons. In the amino terminus, it shows a very high propensity for alpha-helicity, suggesting coiled-coil and possibly a higher order oligomeric arrangement. In the carboxyl terminus, there is a unique SH3 sequence. In Northern blotting, a major 3.7-kilobase and a minor 7.2-kilobase transcript was detected in most chicken tissues. In immunofluorescence microscopy and immunoelectron microscopy on cultured chicken fibroblasts, the protein was localized to focal adhesions in which it showed a distinct codistribution with the focal adhesion proteins vinculin, talin, and paxillin. Phosphoamino acid analysis showed that in cultured chicken heart fibroblasts, the protein contains phosphoserine, but no phosphothreonine or phosphotyrosine, and that the phosphorylation is not dependent on fibronectin. We propose this protein the name FAP52, for Focal Adhesion Protein of 52 kDa, and suggest that it forms part of the multimolecular complex constituting focal adhesion sites.
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PMID:FAP52, a novel, SH3 domain-containing focal adhesion protein. 928 37

Adhesion, spreading, and focal contact formation of primary bone-derived cells on quartz surfaces grafted with a 15 amino acid peptide that contained a -RGD-(-Arg-Gly-Asp-) sequence unique to bone sialoprotein was investigated. The peptide surfaces were fabricated by using a heterbifunctional crosslinker, sulfosuccinimidyal 4-(N-maleimidomethyl)cyclohexane-1-carboxylate, to link the peptide to amine functionalized quartz surfaces. Contact angle measurements, spectroscopic ellipsometry, and X-ray photoelectron spectroscopy were used to confirm the chemistry and thickness of the overlayers. A radial flow apparatus was used to characterize cell detachment from peptide-grafted surfaces. After 20 min of cell incubation, the strength of cell adhesion was significantly (p < 0.05) higher on the -RGD- compared to -RGE- (control) surfaces. Furthermore, the mean area of cells contacting the -RGD- was significantly (p < 0.05) higher than -RGE- surfaces. Vinculin staining showed formation of small focal contact patches on the periphery of bone cells incubated for 2 h on the -RGD- surfaces; however, few or no focal contacts were formed by cells seeded on the -RGE-grafted surfaces. The methods of peptide immobilization utilized in this study can be applied to implants, biosensors, and diagnostic devices that require specificity in cell adhesion.
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PMID:The detachment strength and morphology of bone cells contacting materials modified with a peptide sequence found within bone sialoprotein. 933 44

Mitotic cells typically lack well-formed focal adhesions. As an approach to explore the dynamic process regulating the focal adhesion assembly, we examined states of focal adhesion proteins during mitosis of the cell cycle. We found that the amount of paxillin was significantly reduced during mitosis of the cell cycle, whereas other focal adhesion proteins including talin, vinculin and Focal Adhesion Kinase did not. Proteolytic degradation appeared to be involved in the mitotic reduction, but transcriptional and/or translational controls of the mRNA were not essential for this downregulation. Moreover, concurrent with the decreased protein level, phosphorylation status of paxillin altered during mitosis; mitotic paxillin was phosphorylated primarily on serine and dephosphorylated on tyrosine while interphase one was phosphorylated both on serine and tyrosine. We found that mitotic phosphorylation created an electrophoretically slow-migrating population of paxillin which was barely detected in interphase cells. This mitotic specific modification occurred with both alpha and beta isoforms of paxillin. We also examined the fate of paxillin protein by changing its protein amount. We found that majority of paxillin overexpressed was subjected to the specific modification but not to the downregulation in the mitotic arrested cells. On the other hand, paxillin exogenously expressed at a moderate level was subjected to both the mitotic modification and downregulation. Collectively, we concluded that paxillin's specific serine phosphorylation together with the proteolytic downregulation of a limited fraction of paxillin is taken place during the mitosis of the cell cycle.
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PMID:Mitosis specific serine phosphorylation and downregulation of one of the focal adhesion protein, paxillin. 936 41

The rat L6 skeletal muscle cell line was used to study expression of the dystrophin-containing glycoprotein complex and its interaction with the integrin system involved in the cell-matrix adhesion reaction. A complex of dystrophin and its associated proteins was fully expressed in L6 myotubes, from which anti-dystrophin or anti-alpha-sarcoglycan co-precipitated integrin alpha 5 beta 1 and other focal adhesion-associated proteins vinculin, talin, paxillin, and focal adhesion kinase. Immunostaining and confocal microscopy revealed that dystrophin, alpha-sarcoglycan, integrin alpha 5 beta 1, and vinculin exhibited overlapping distribution in the sarcolemma, especially at focal adhesion-like, spotty structures. Adhesion of cells to fibronectin- or collagen type I-coated dishes resulted in induction of tyrosine phosphorylation of alpha- and gamma-sarcoglycans but not beta-sarcoglycan. The same proteins were also tyrosine-phosphorylated when L6 cells in suspension were exposed to Arg-Gly-Asp-Ser peptide. All of these tyrosine phosphorylations were inhibited by herbimycin A. On the other hand, treatment of L6 myotubes with alpha- and gamma-sarcoglycan antisense oligodeoxynucleotides resulted in complete disappearance of alpha- and gamma-sarcoglycans and in significant reduction of levels of the associated focal adhesion proteins, which caused about 50% reduction of cell adhesion. These results indicate the existence of bidirectional communication between the dystrophin-containing complex and the integrin adhesion system in cultured L6 myocytes.
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PMID:Bidirectional signaling between sarcoglycans and the integrin adhesion system in cultured L6 myocytes. 943 Jun 99

The ubiquitously expressed Na-H exchanger NHE1 functions in regulating intracellular pH and cell volume. NHE1 activity is stimulated by hormones, growth factors, and activation of integrin receptors. We recently determined that NHE1 activity is also stimulated by activation of the low molecular weight GTPase RhoA and that increases in NHE1 activity are necessary for RhoA-induced formation of actin stress fibers. We now show that NHE1 acts downstream of RhoA to modulate initial steps in integrin signaling for the assembly of focal adhesions. Adhesion of CCL39 fibroblasts on fibronectin was markedly delayed in the presence of the NHE inhibitor ethylisopropylamiloride. In mutant PS120 cells, derived from CCL39 fibroblasts but lacking NHE1, adhesion was also delayed but was rescued in PS120 cells stably expressing NHE1. In the absence of NHE1 activity, cell spreading was inhibited, and the accumulation of integrins, paxillin, and vinculin at focal contacts was impaired. Additionally, tyrosine phosphorylation of p125(FAK) induced by integrin clustering was also impaired. Inactivation of RhoA with C3 transferase and inhibition of the Rho-kinase p160ROCK with the pyridine derivative Y-27632 completely abolished activation of NHE1 by integrins but not by platelet-derived growth factor. These findings indicate that NHE1 acts downstream of RhoA to contribute a previously unrecognized critical signal to proximal events in integrin-induced cytoskeletal reorganization.
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PMID:Na-H exchange acts downstream of RhoA to regulate integrin-induced cell adhesion and spreading. 969 82

This study investigated in vitro the effect of therapeutic ultrasound (ULS) on smooth muscle cell (SMC) function as adhesion, migration and proliferation. Experiments were conducted on aortic SMC in culture. The LD50 was established (1.5 W for 15 s at a frequency of 20 kHz) and used as standard dose in all experiments. Control SMC and viable sonicated SMC were compared in each experiment. Migratory capacity decreased 2.4-fold after sonication and stayed reduced for up to 24 h. Adhesion capacity decreased 5.5-fold after ULS. The proliferative capacity was similar to that of nonsonicated SMC. Sonication was accompanied by the disorganization of alpha-SM actin fibers and diminished distribution of vinculin; tyrosinated alpha tubulin and vimentin appeared unaffected. These changes might be responsible for the observed inhibition of SMC adhesion and migration. Sonicated cells exhibited less lamellipodia, membrane collapse and bleb formation. The signal transduction cascade, which involves activation of the phospholipase-C pathway, was unaffected by ULS.
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PMID:Ultrasound inhibits the adhesion and migration of smooth muscle cells in vitro. 969 75

Patients infected with the malaria parasite Plasmodium falciparum may develop a diffuse reversible encephalopathy, termed cerebral malaria. It is unclear how the intraerythrocytic parasite, which sequesters in the cerebral microvasculature but does not enter the brain parenchyma, induces this neurological syndrome. Adhesion of parasitized red blood cells in the brain microvasculature is mediated by specific receptors on the host endothelium, including intercellular adhesion molecule (ICAM)-1, CD36 and CD31. Leucocyte binding to cerebral endothelial cells in culture induces intracellular signalling via ICAM-1. The hypothesis that parasitized red blood cells binding to receptors on cerebral endothelial cells causes changes in the integrity of the blood-brain barrier was tested. Immunohistochemistry was used to examine the blood-brain barrier in human cerebral malaria, with antibodies to macrophage and endothelial activation markers, intercellular junction proteins, and plasma proteins. The distribution of the cell junction proteins occludin, vinculin and ZO-1 were altered in cerebral malaria cases compared to controls. While fibrinogen was the only plasma protein detected in the perivascular space, there was widespread perivascular macrophage activation, suggesting that these cells had been exposed to plasma proteins. It was concluded that functional changes to the blood-brain barrier occur in cerebral malaria, possibly as a result of the binding of parasitized red blood cells to cerebral endothelial cells. These changes require further examination in vitro.
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PMID:Evidence of blood-brain barrier dysfunction in human cerebral malaria. 1047 50


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