Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adherence of the opportunistic pathogen Candida albicans to basement membrane (BM) proteins is considered a crucial step in the development of candidiasis. In this study the interactions of C. albicans yeast cells with the three main domains of type IV collagen, a major BM glycoprotein, were analysed. C. albicans adhered to the three immobilized domains by different mechanisms. Adhesion to the N-terminal cross-linking domain (7S) required the presence of divalent cations, whereas interaction with the central collagenous domain (CC) was cation-independent. Recognition of the C-terminal non-collagenous domain (NC1) was partially cation-dependent. Binding inhibition assays with the corresponding domains in soluble form showed that these interactions were specific. Both Ca(2+) and Mg(2+) promoted adhesion to the 7S domain and the interaction was completely abolished by EDTA. Treatment of the 7S domain, or its subunits, with N-glycosidase F reduced yeast binding by approximately 70%. Moreover, several sugars known to be part of the N-linked oligosaccharide chains of collagen IV inhibited adhesion to immobilized 7S; N-acetylglucosamine, L-fucose and methylmannoside caused a similar inhibition whereas N-acetyllactosamine was a more effective inhibitor. In contrast, glucose, galactose, lactose or heparan sulfate did not affect yeast binding. Combinations of the inhibitory sugars at suboptimal inhibition concentrations did not reduce C. albicans adhesion more than the individual sugars, pointing to a single lectin as responsible for the interaction. These results taken together show that C. albicans utilizes several adhesins for interacting with type IV collagen, and that at least one of them is a lectin which recognizes the 7S(IV) oligosaccharide residues as its receptor.
 ...
PMID:Different adhesins for type IV collagen on Candida albicans: identification of a lectin-like adhesin recognizing the 7S(IV) domain. 1142 74

Engagement of adhesion molecules on monocytes and other myeloid leukocytes, which are effector cells of the innate immune system, not only tethers the leukocytes in place but also transmits outside-in signals that induce functional changes and alter gene expression. We found that a subset of mRNAs that are induced or amplified by adhesion of human monocytes to P-selectin via its surface ligand, P-selectin glycoprotein 1, have characteristics that suggest specialized translational control. One of these codes for urokinase plasminogen activator receptor (UPAR), a critical surface protease receptor and regulator of cell adhesion and migration. Although UPAR transcripts are induced by adhesion, rapid synthesis of the protein uses constitutive mRNA without a requirement for new transcription and is regulated by mammalian target of rapamycin, demonstrating new biologic roles for the signal-dependent translation pathway controlled by this intracellular kinase. The synthesis of UPAR in monocytic cells is also regulated by eukaryotic translation initiation factor 4E, a second key translational checkpoint, and phosphorylation of eukaryotic translation initiation factor 4E is induced by adhesion of monocytes to P-selectin. Translationally controlled display of UPAR by monocytes confers recognition of the matrix protein, vitronectin. Adhesion-dependent signaling from the plasma membrane to translational checkpoints represents a previously unrecognized mechanism for regulating surface phenotype that may be particularly important for myeloid leukocytes and other cells that are specialized for rapid inflammatory and vascular responses.
 ...
PMID:Cell adhesion regulates gene expression at translational checkpoints in human myeloid leukocytes. 1151 14

The oxytocinergic system, which plays a major role in the control of different aspects of maternity, undergoes extensive synaptic and neuronal-glial remodelling during parturition and lactation and has thus become a remarkable example of activity-dependent morphological synaptic plasticity in the adult mammalian brain. The use of different comparative ultrastructural analyses on the rat supraoptic and paraventricular nuclei, together with identification of pre- and post-synaptic elements, has allowed us to show that there is a significant increase in the number of GABAergic, glutamatergic and noradrenergic synapses impinging on oxytocin neurons, concomitant with a reduction of glial coverage of the neurons. This synaptic plasticity involves axo-dendritic and axo-somatic contacts originating from terminals making one or several synaptic contacts in one plane of section. While noradrenergic afferents arise from medullary catecholaminergic neurons, our recent in vitro observations indicate that GABAergic and glutamatergic afferents derive, at least partly, from local intrahypothalamic neurons, in close proximity to oxytocin neurons. The cellular mechanisms underlying this morphological synaptic plasticity remain to be determined but it is highly likely that they depend on increased activity in both pre- and post-synaptic elements. Moreover, the oxytocin system continues to express 'embryonic' molecular features that may allow the morphological plasticity to occur. In particular, it expresses high levels of cell surface adhesion molecules currently thought to intervene in synaptic remodelling in the developing and lesioned central nervous system, including the weakly adhesive polysialylated isoform of the Neural Cell Adhesion Molecule, the axonal glycoprotein F3 and its ligand, the extracellular matrix glycoprotein, tenascin-C.
 ...
PMID:Maternity leads to morphological synaptic plasticity in the oxytocin system. 1158 44

Skin-homing T cells are defined by the expression of the cutaneous lymphocyte-associated antigen (CLA) which enables the cells to selectively bind to vascular endothelial E-selectin close to sites of cutaneous inflammation, an initial step in the effective extravasation from blood into the inflamed tissue. Essentially all CLA on T cells decorates the backbone of the P-selectin glycoprotein ligand-1 (PSGL-1). In this study we show that human peripheral blood B cells (PBBC) and tonsillar B cells (TBC) do not display PSGL-1 in fluorescence-activated cell sorter analysis using different murine monoclonal antibodies and polyclonal rabbit anti-PSGL-1 antiserum. A significant population of TBC, however, expresses a HECA-452-reactive epitope. These cells represent nonactivated IgM(+)/IgG(-) mature B lymphocytes. Up to 50% of the TBC in a given preparation strongly bind to E- and up to 79% to P-selectin. The shear stress resistance in a parallel-plate flow chamber system was high. Neuraminidase treatment of TBC totally and O-sialoglycoprotein endopeptidase partially diminished HECA-452 reactivity and reduced E- but not P-selectin ligand activities. Mocarhagin had no effect in the assays. The data suggest a different ligand for P-selectin and a distinct glycoprotein carrier for the E-selectin ligand as compared to T cells or other leukocytes. Adhesion to P-selectin, however, still required sulfation of the ligand for function. Western blots of TBC cell lysates detected a >240-kD HECA-452-reactive material that was resistant to reducing conditions. Anti-PSGL-1 did not reveal immunoreactive material in these cell lysates. B cell activation did neither significantly change HECA positivity nor induce PSGL-1 expression. Cultured, activated TBC, however, maintained expression of the integrin alpha4beta7. Human peripheral blood B cells had similar cell surface characteristics to TBC. Our observations suggest that several adhesion molecules may be involved in B cell homing which include CLA, the P-selectin ligand, and structures such as alpha4beta7.
 ...
PMID:Tonsillar B cells do not express PSGL-1, but a significant fraction displays the cutaneous lymphocyte antigen and exhibits effective E- and P-selectin ligand activity. 1164 9

A novel disintegrin, saxatilin, was purified from Korean snake (Gloydius saxatilis) venom by means of chromatographic fractionations. We have also isolated the cDNA encoding the disintegrin using cDNA library of the snake venom gland and analyzed its complete nucleotide sequence. Saxatilin is a single-chain polypeptide composed of 73 amino acids including 12 cysteines as well as the tripeptide sequence Arg-Gly-Asp (RGD), a proposed recognition site of adhesive proteins. Molecular mass of saxatilin was determined to be 7712 Da by matrix-assisted laser desorption ionization mass spectrometry. Saxatilin inhibits glycoprotein (GP) IIb-IIIa binding to immobilized fibrinogen with IC(50) of 2.0 nM and ADP-induced platelet aggregation with IC(50) of 127 nM, respectively. The snake venom disintegrin also significantly suppresses basic fibroblast growth factor-induced human umbilical vein endothelial cell (HUVEC) proliferation, but has little effect on normal growth of the cell. Interaction of human umbilical vein cell to immobilized vitronectin is also inhibited by binding of saxatilin to alpha(v)beta(3) integrin. Adhesion of smooth muscle cells (SMCs) to vitronectin as well as vitronectin-induced migration of the cells was strongly inhibited by saxatilin. Several lines of experimental evidence suggest potential use of saxatilin for development of therapeutic agents.
 ...
PMID:Snake venom disintegrin, saxatilin, inhibits platelet aggregation, human umbilical vein endothelial cell proliferation, and smooth muscle cell migration. 1186 11

Fibrillins are the major glycoprotein components of microfibrils that form a template for tropoelastin during elastic fibrillogenesis. We have examined cell adhesion to assembled purified microfibrils, and its molecular basis. Human dermal fibroblasts exhibited Arg-Gly-Asp and cation-dependent adhesion to microfibrils and recombinant fibrillin-1 protein fragments. Strong integrin alpha 5 beta 1 interactions with fibrillin ligands were identified, but integrin alpha v beta 3 also contributed to cell adhesion. Fluorescence-activated cell sorting analysis confirmed the presence of abundant alpha 5 beta 1 and some alpha v beta 3 receptors on these cells. Adhesion to microfibrils and to Arg-Gly-Asp containing fibrillin-1 protein fragments induced signaling events that led to cell spreading, altered cytoskeletal organization, and enhanced extracellular fibrillin-1 deposition. Differences in cell shape when plated on fibrillin or fibronectin implied substrate-specific alpha 5 beta 1-mediated cellular responses. An Arg-Gly-Asp-independent cell adhesion sequence was also identified within fibrillin-1. Adhesion and spreading of smooth muscle cells on fibrillin ligands was enhanced by antibody-induced beta1 integrin activation. A375-SM melanoma cells bound Arg-Gly-Asp-containing fibrillin-1 protein fragments mainly through alpha v beta 3, whereas HT1080 cells used mainly alpha 5 beta 1. This study has shown that fibrillin microfibrils mediate cell adhesion, that alpha 5 beta 1 and alpha v beta 3 are both important but cell-specific fibrillin-1 receptors, and that cellular interactions with fibrillin-1 influence cell behavior.
 ...
PMID:Cell adhesion to fibrillin-1 molecules and microfibrils is mediated by alpha 5 beta 1 and alpha v beta 3 integrins. 1280 87

Acute thrombotic arterial occlusion is the leading cause of morbidity and mortality in the Western world. Von Willebrand factor is thought to be the only indispensable adhesive substrate to promote thrombus formation in high shear environments. We found that thrombospondin-1, a glycoprotein enriched in arteriosclerotic plaques, might function as an alternative substrate for thrombus formation. Platelets adhered to thrombospondin-1 in a shear dependent manner with an optimum shear as found in stenosed arteries. Adhesion is extremely firm, with no detachment of platelets up to a shear rate of 4000 s(-1). Experiments using platelets from a patient completely lacking von Willebrand factor showed that von Willebrand factor is not involved in platelet binding to thrombospondin-1. Platelet adhesion to thrombospondin-1 is not mediated via beta3-integrins or GPIa. CD36 partially mediates the adhesion of pre-activated platelets. We identified GPIb as high shear adhesion-receptor for thrombospondin-1. Soluble GPIb, as well as antibodies against the GPIb, blocked platelet adhesion almost completely. The new discovered thrombospondin-1-GPIb adhesion axis under arterial shear conditions might be important, not only during thrombus formation but also for pathological processes where other cells bind to the endothelium or subendothelium, including arteriosclerosis, inflammation and tumor metastasis, and a promising therapeutic target.
 ...
PMID:Thrombospondin-1 mediates platelet adhesion at high shear via glycoprotein Ib (GPIb): an alternative/backup mechanism to von Willebrand factor. 1282 98

A macroarray approach used to list genes differentially expressed in goat mammary gland (gestation vs. lactation), other than milk protein genes, allowed us to detect the Glycosylation-dependent Cell Adhesion Molecule 1 (GLYCAM1) gene. GLYCAM1, a member of the glycoprotein mucin family, is a component of the milk fat globule membrane (MFGM). Its complete cDNA and gene sequences were determined and it was mapped by fluorescent in situ hybridization (FISH) on goat and cattle chromosome 5 (CHI5q21 and BTA5q21), and on sheep chromosome 3 (OAR3q21). Northern blot analyses confirmed its differential expression during the development and differentiation of the mammary gland of ruminants with a significantly higher mRNA amount during lactation than during pregnancy. An experimental in vivo induction model for lactation, developed by Kann et al., showed that the expression of GLYCAM1 is hormonally regulated in the mammary gland of ewes. Interspecies comparison of the gene promoter revealed the evolutionary conservation of a short proximal nucleotide sequence encompassing several transcription factor binding sites that could mediate the above-mentioned hormonal regulation.
 ...
PMID:Structure and expression of goat GLYCAM1 gene: lactogenic-dependent expression in ruminant mammary gland and interspecies conservation of the proximal promoter. 1295 79

Inflammation is a defensive reaction of an organism in response to injuring factors and is characterised by effector cells infiltration. Adhesion molecules are involved in their ordered influx. These molecules are glycoprotein particles present on cell surface and on intracellular matrix proteins. Cytokines, chemokines and other inflammatory process mediators modulate the expression of adhesion molecules. Anti-adhesion therapy involves many techniques. Most frequently monoclonal antibodies are used. Other forms of therapy contribute to blocking the synthesis of molecules at transcription level or to inhibition of their transfer from cell interior to its surface. Soluble molecule forms or their receptors are also applied.
 ...
PMID:[The importance of inhibition of adhesion molecules in allergic inflammation]. 1452 55

Rat sperm surface antigen Sperm Adhesion Molecule1, SPAM1 (a.k.a. 2B1 or PH-20) is a plasma membrane-bound glycoprotein with hyaluronidase activity and putative roles during fertilization. Previously the antigen was thought to be testis-specific but recently it has been shown to be synthesized in the epididymis (mouse, macaque and human). Using the efferent ductule ligated (EDL) rat as a model to produce a sperm-free androgen-maintained epididymis, we have examined the factors regulating the expression of epididymal 2B1. RT-PCR and in situ transcript hybridization (ISH) studies showed that 2B1 mRNA is transcribed in the principal cells in all three regions of the epididymis. Its cognate protein was also detected by Western blot analysis in sperm-free cytosols from normal epididymis and found to undergo endoproteolytic cleavage into 2 subunits of similar size to the sperm-bound form. Immunohistochemistry with a monoclonal antibody to 2B1 confirmed that the protein is present in the epididymal epithelium and luminal secretions. The intensity of staining was much stronger in the sperm-free EDL epididymis than that in the normal (sperm-present) epididymis. The protein was shown to have hyaluronidase activity at neutral pH and both its quantity and activity appeared to be greater in the EDL epididymis. It is suggested that a soluble form of SPAM1 glycoprotein is synthesized and released in the epididymis and that in addition to androgens, its regulation may involve a cross-talk between the tubule epithelium and lumicrine factors, the latter possibly of testicular origin.
 ...
PMID:Expression and secretion of rat SPAM1(2B1 or PH-20) in the epididymis: role of testicular lumicrine factors. 1506 58


<< Previous 1 2 3 4 5 6 7 8 9 10