Disease relevance of Intercellular Junctions

• gamma-Cleavage-Independent Functions of Presenilin, Nicastrin, and Aph-1 Regulate Cell-Junction Organization and Prevent Tau Toxicity In Vivo [1].
• This study was performed to determine whether hypoxia in glucose-free solutions can increase the electrical resistance of intercellular junctions in ventricular muscle [2].
• Our study shows that PKD1 colocalizes with E-cadherin at cell junctions in LNCaP prostate cancer cells and coimmunoprecipitates with E-cadherin from lysates of LNCaP cells [3].
• The cell surface and intercellular junctions of transformed and non-transformed hybrid cells, obtained from fusion of murine mammary adenocarcinoma cells (TA3B) and normal rat embryofibroblasts (REF), were compared with those of the parental cells, using ruthenium red (RR) staining of cells fixed in situ [4].
• We isolated molecular clones of the provirus-host cell junctions (tumor junction fragments) from two avian leukosis virus-induced lymphomas and compared the structures of these clones with a clone of the normal c-myc gene [5].

High impact information on Intercellular Junctions

• Membrane-associated guanylate kinases regulate adhesion and plasticity at cell junctions [6].
• In lens cells these junctions contain A-CAM, while the same type of intercellular junctions in liver cells contain another cell adhesion molecule, L-CAM [7].
• A glycoprotein involved in aggregation of D. discoideum is distributed on the cell surface in a nonrandom fashion favoring cell junctions [8].
• Calcium ion produces graded changes in permeability of membrane channels in cell junction [9].
• Supporting a role for CD2AP in the specialized cell junction known as the slit diaphragm, CD2AP associated with nephrin, the primary component of the slit diaphragm [10].

Chemical compound and disease context of Intercellular Junctions

• We have previously identified a human receptor protein tyrosine phosphatase of the MAM domain family, termed PCP-2, in human pancreatic adenocarcinoma cells and found that this protein was colocalized with beta-catenin and E-cadherin at cell junctions [Wang, H.-Y., et al. (1996) Oncogene 12, 2555-2562] [11].
• Treatment of confluent monolayers of Caco-2 cells with ethylene glycol-bis(beta-aminoethyl ether)- N,N,N1,N1-tetraacetic acid (EGTA), which disrupts intercellular junctions, greatly reduced the uptake of Listeria cells [12].
• In this study the morphology of intercellular junctions in a murine mammary adenocarcinoma and in a solid carcinoma which resulted from continuous transplantations of this spontaneous tumor are described employing the techniques of ultrathin-sectioning after conventional fixation and tannic acid fixation and freeze-fracturing [13].

Biological context of Intercellular Junctions

• Organization of cells into tissues requires loss of cell motility, formation of specialized membrane domains and assembly of cell junctions, which are all activities potentially involving spectrin [14].
• Discs large (Dlg) was the first identified member of an increasingly important class of proteins called membrane-associated guanylate kinase homologs (MAGUKs), which are often concentrated at cell junctions and contain distinct peptide domains named PDZ1-3, SH3, HOOK, and GUK [15].
• Our data support the model that during podocyte intercellular junction formation, engagement of the nephrin ectodomain induces transient Fyn catalytic activity that results in nephrin phosphorylation on specific nephrin cytoplasmic domain tyrosine residues [16].
• Transgene expression was associated with loss of Connexin 26 and Connexin 30 from epidermal keratinocyte intercellular junctions and accumulation in cytoplasm [17].
• We propose that LIN-2A is required for the localization of one or more signal transduction proteins (such as LET-23) to either the basal membrane domain or the cell junctions, and that mislocalization of signal transduction proteins in lin-2 mutants interferes with vulval induction [18].

Anatomical context of Intercellular Junctions

• The resultant tumors display lumen-like morphology, contain carcinoma-like focal areas with intercellular junctions resembling desmosomes, and coexpress epithelial (cytokeratin) and mesenchymal (vimentin) cytoskeletal markers [19].
• The sequence is homologous to mammalian plakoglobin, a protein of desmosomal and zonula adherens cell junctions, and to the plakoglobin homolog in Drosophila melanogaster, the product of the segment polarity gene armadillo [20].
• Here, we show that VAB-9 requires HMR-1/cadherin for localization to the cell membrane, and both HMP-1/alpha-catenin and HMP-2/beta-catenin for maintaining its distribution at the cell junction [21].
• Upon calcium repletion, occludin, zonula occludens 1, and E-cadherin failed to redistribute to the intercellular junctions; assembly of the apical F-actin cytoskeleton was prevented; and barrier function failed to recover [22].
• We report here the identification of a novel protein (junctional adhesion molecule [JAM]) that is selectively concentrated at intercellular junctions of endothelial and epithelial cells of different origins [23].

Associations of Intercellular Junctions with chemical compounds

• This transcellular pathway is selective, as it conducts thiourea, but not glycerol and mannitol, demonstrating that it is not due to a loosening of intercellular junctions [24].
• We also observed a disruption of the normal pattern of the actin-cytoskeleton, particularly in the area of cell to cell junctions, as demonstrated by fluorescent staining of f-actin with rhodamine phallicidin [25].
• We show here that beta-catenin, gamma-catenin/plakoglobin, and p120-Cas are all significantly tyrosine phosphorylated in primary mouse keratinocytes induced to differentiate by calcium, with a time course similar to that of cell junction formation [26].
• Whole epithelial sheets were glycerinated, which leaves the brush border and intercellular junctions intact, and then treated with ATP, PPi, ITP, ADP, GTP, or delta S-ATP [27].
• Distribution of sterol-specific complexes in a continually shearing region of a plasma membrane and at procaryotic-eucaryotic cell junctions [28].

Gene context of Intercellular Junctions

• One such gene, egl-8, encodes a phospholipase Cbeta that is present throughout the nervous system and near intestinal cell junctions [29].
• Mutations in vab-9 enhance adhesion defects through functional loss of the cell junction genes apical junction molecule 1 (ajm-1) and discs large 1 (dlg-1), suggesting that VAB-9 is involved in cell adhesion [21].
• PECAM-1 is a 130-120-kD integral membrane glycoprotein found on the surface of platelets, at endothelial intercellular junctions in culture, and on cells of myeloid lineage [30].
• Plakoglobin (gamma-catenin), a member of the armadillo family of proteins, is a constituent of the cytoplasmic plaque of desmosomes as well as of other adhering cell junctions, and is involved in anchorage of cytoskeletal filaments to specific cadherins [31].
• The lipid phosphatase activity of PTEN is critical for stabilizing intercellular junctions and reverting invasiveness [32].

Analytical, diagnostic and therapeutic context of Intercellular Junctions

• Confocal microscopy localized TSP within intercellular junctions between aggregated MCF-7 cells in suspension [33].
• Microinjection of SmgGDS cDNA into CHO cells stably expressing HA-RhoA causes HA-RhoA to be excluded from the nucleus and cell junctions, similar to the distribution of RhoA(Asn-19) [34].
• Immunocytochemistry revealed that phenylarsine oxide rapidly stimulated the tyrosine phosphorylation of proteins associated with intercellular junctions [35].
• Silver staining and "gap-FRAP" experiments suggest that 12(S)-HETE altered the normally apposed cell junctions and impaired gap junction-mediated cell-cell communication [36].
• Immunofluorescence shows that H(2)O(2) exposure caused a loss of pan-reactive cadherin and beta-catenin from cell junctions that was not blocked by the src kinase inhibitor PP1 [37].

References