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Cell Adhesion Sites (cell + adhesion_site)
Selected AbstractsSynthesis of heterotrimeric collagen peptides containing the ,1,1 integrin recognition site of collagen type IVJOURNAL OF PEPTIDE SCIENCE, Issue 5 2002Barbara Saccá Abstract Collagen type IV provides a biomechanically stable scaffold into which the other constituents of basement membranes are incorporated, but it also plays an important role in cell adhesion. This occurs with collagen type IV mainly via the ,1,1 integrin, and the proposed epitope involved in this type of collagen/integrin interaction corresponds to a non-sequential R/Xaa/D motif, where the arginine and aspartate residues are provided by the ,2 and ,1 chains of the collagen molecule, respectively. Since the stagger of the three , chains in native collagen type IV is still unknown and different alignments of the chains lead to different spatial epitopes, two heterotrimeric collagen peptides containing the natural 457,469 sequences of the cell adhesion site were synthesized in which the single chains were assembled via disulfide bonds into the two most plausible ,1,2,1, and ,2,1,1, registers. The differentiated triple-helical stabilities of the two heterotrimers suggest a significant structural role of the chain register in collagen, although the binding to ,1,1 integrin is apparently less affected as indicated by preliminary experiments. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source] Novel role of nectin: implication in the co-localization of JAM-A and claudin-1 at the same cell,cell adhesion membrane domainGENES TO CELLS, Issue 8 2008Kaori Kuramitsu Tight junctions (TJs) are formed at the apical side of adherens junctions (AJs) in epithelial cells. Major cell adhesion molecules (CAMs) at TJs are JAM and claudin, whereas major CAMs at AJs are nectin and cadherin. We previously showed that nectin initially forms cell,cell adhesion and then recruits cadherin to the nectin-based cell,cell adhesion sites to form AJs, followed by the recruitment of JAM and claudin to the apical side of AJs to form TJs. We investigated the roles of nectin in the formation of TJs by expressing various combinations of CAMs in L fibroblasts with no TJs or AJs. Co-expression of one of the AJ CAMs and one of the TJ CAMs formed two separate cell,cell adhesion membrane domains (CAMDs). Co-expression of nectin-3 and E-cadherin formed the same CAMD, but co-expression of JAM-A and claudin-1 did not form the same CAMD. Co-expression of JAM-A and claudin-1 with nectin-3, but not E-cadherin, made them form the same CAMD, which was separated from the nectin-based CAMD. Nectin-3 required afadin, a nectin- and F-actin-binding protein, for this ability. In conclusion, nectin plays a novel role in the co-localization of JAM and claudin at the same CAMD. [source] Involvement of integrin-induced activation of protein kinase C in the formation of adherens junctionsGENES TO CELLS, Issue 5 2007Misa Ozaki In epithelial cells, tight junctions (TJs) and adherens junctions (AJs) form junctional complexes. At AJs, cadherins and nectins are the major cell-cell adhesion molecules. Nectins first form cell,cell adhesions and then recruit cadherins to the nectin-based cell,cell adhesion sites to form AJs in coordination with the activation of integrin ,v,3, followed by the formation of TJs. We previously demonstrated that when MDCK cells precultured at a low Ca2+ concentration were treated with the protein kinase C (PKC) activator 12- O -tetradecanoyl-phorbol-13-acetate (TPA), incomplete AJs and a TJ-like structure were achieved. However, it remains unknown how PKC is activated and how it regulates the formation of cell,cell junctions. When MDCK cells precultured at a low Ca2+ concentration were treated with TPA, incomplete AJs were formed without the activation of integrin ,v,3. Treatment of cells with TPA also enhanced the phosphorylation of FAK, which transmits the outside-in signal of integrin and plays a role in the nectin-induced formation of AJs. In addition, inhibition of PKC suppressed the formation of AJs. These results indicate that the activation of PKC functions downstream of integrin ,v,3 and upstream of FAK, and is important for the nectin-induced formation of AJs. [source] Roles of cell adhesion molecules nectin and nectin-like molecule-5 in the regulation of cell movement and proliferationJOURNAL OF MICROSCOPY, Issue 3 2008H. OGITA Summary In response to chemoattractants, migrating cells form protrusions, such as lamellipodia and filopodia, and structures, such as ruffles over lamellipodia, focal complexes and focal adhesions at leading edges. The formation of these leading edge structures is essential for directional cell movement. Nectin-like molecule-5 (Necl-5) interacts in cis with PDGF receptor and integrin ,v,3, and enhances the activation of signalling molecules associated with these transmembrane proteins, which results in the formation of leading edge structures and enhancement of directional cell movement. When migrating cells come into contact with each other, cell,cell adhesion is initiated, resulting in reduced cell velocity. Necl-5 first interacts in trans with nectin-3. This interaction is transient and induces down-regulation of Necl-5 expression at the cell surface, resulting in reduced cell movement. Cell proliferation is also suppressed by the down-regulation of Necl-5, because the inhibitory effect of Necl-5 on Sprouty2, a negative regulator of the Ras signalling, is diminished. PDGF receptor and integrin ,v,3, which have interacted with Necl-5, then form a complex with nectin, which initiates cell,cell adhesion and recruits cadherin to the nectin-based cell,cell adhesion sites to form stable adherens junctions. The formation of adherens junctions stops cell movement, in part through inactivation of integrin ,v,3 caused by the trans -interaction of nectin. Thus, nectin and Necl-5 play key roles in the regulation of cell movement and proliferation. [source] Participation of protein kinase C , isoform and extracellular signal-regulated kinase in neurite outgrowth of GT1 hypothalamic neuronsJOURNAL OF NEUROCHEMISTRY, Issue 6 2002Youngshik Choe Abstract In the present study, we investigated the selective role of protein kinase C (PKC) isoforms on neurite outgrowth of the GT1 hypothalamic neurons using several PKC isoform-selective inhibitors and transfection-based expression of enhanced green fluorescence protein (EGFP)-fused PKC isoforms. 12- O -Tetradecanoylphorbol-13-acetate (TPA) induced neurite outgrowth and growth cone formation, effects that were blocked by GF 109203X (a PKC inhibitor), safingolTM(a PKC,-selective inhibitor), but not by rottlerinTM (a PKC,-selective inhibitor), indicating that PKC, may be selectively involved in neurite outgrowth and cytoskeletal changes of filamentous actin and ,-tubulin. To define the differential localization of PKC isoforms, EGFP-tagged PKC,, PKC,, and PKC, were transfected into GT1 neuronal cells. TPA treatment induced relocalization of PKC,-EGFP to growth cones and cell,cell adhesion sites, PKC,-EGFP to the nucleus, and PKC,-EGFP to the membrane ruffle, respectively. An EGFP chimera of the catalytic domain of PKC, (PKC,-Cat-EGFP), the expression of which was inducible by doxycycline, was employed to directly ascertain the effect of PKC, enzymatic activity on neurite outgrowth of GT1 cells. Transient transfection of PKC,-Cat-EGFP alone increased the neurite-outgrowth and doxycycline treatment further augmented the number of neurite-containing cells. We also examined the involvement of the extracellular signal-regulated kinase (ERK) MAP kinase in TPA-induced neurite outgrowth. TPA treatment increased phosphorylated ERK MAP kinase, but not p38 MAP kinase. Specific inhibition of PKC, with safingol blocked the phosphorylation of ERK induced by TPA. More importantly, both neurite outgrowth and phosphorylation of ERK by TPA were blocked by PD 098059, a specific inhibitor of MEK (MAP kinase/ERK kinase-1), but not by SB203580, a specific inhibitor of p38 MAP kinase. These results demonstrate that PKC, isoform-specific activation is involved in neurite outgrowth of GT1 hypothalamic neuronal cells via ERK, but not the p38 MAP kinase signal pathway. [source] | ||||||||||