B Geiger

..Are cells using stretch-activated ion channels to explore the extracellular environment surrounding them, or do they use for that purpose the submembrane protein network that interconnects integrin receptors with the actin cytoskeleton?..

..This review describes integrin functions, mechanosensors, molecular switches and signal-transduction pathways activated and integrated by adhesion, with a unifying theme being the importance of local physical forces...

..The molecular mechanisms underlying these processes are discussed...

..We will primarily focus on the adhesion and migration of cancer cells, and their relationships to the deregulated growth, metastatic dissemination, and anchorage independence associated with malignant transformation...

....

..This change promotes phosphorylation of p130Cas by Src family kinases and the transduction of integrin-mediated signaling...

..These findings support the notion that there will be a selective pressure for the loss of wild-type p53 expression in cancers that are driven by excessive accumulation of beta-catenin...

..The results put clear constraints on the possible molecular mechanisms for the mechanosensory response of focal adhesions to applied force...

..These findings demonstrate that Src family kinases, and pp60(c-src) in particular, have a central role in regulating protein dynamics at cell-matrix interfaces, both during early stages of interaction and in mature focal contacts...

..These results suggest that increased cadherin-mediated adhesion and translocation of beta-catenin to adherens junctions are involved in activating the early steps of myogenic differentiation...

....

..Because of its dual effects on the adhesive properties of the cells and its association with fibronectin, galectin-8 might be considered a novel type of matricellular protein...

..These changes are driven by mechanical force generated by the actin- and myosin-containing contractile machinery of the cells, or by external forces applied to the cells, and regulated by matrix rigidity...

..The mechanisms underlying the assembly and reorganization of actin-associated focal adhesions and the involvement of mechanical forces in regulating their dynamic properties are discussed...

....

..We directly observed a volume contraction of 20% with increasing temperature between 1 and 11 degrees C by wet-mode ESEM...

..The growth dynamics is calculated and the predicted sliding of focal adhesions is consistent with several experiments...

..The formation of these adhesions depends on actomyosin contractility and matrix pliability...

....

..These dynamic studies demonstrate that pericellular hyaluronan mediates initial cell-surface adhesion, and regulates the formation of focal adhesions...

..These observations illuminate, for the first time, early stages in focal complex assembly and the dynamic process associated with its transformation into focal adhesion...

..Pro-inflammatory cytokines induce death of pancreatic beta cells, leading to the development of type 1 diabetes. We sought to identify novel players and the underlying mechanisms involved in this process...

..Here, we address different aspects of multidimensional microscopy and, in particular, image quantification and the characterization of molecular dynamics, as applied to the study of cell adhesion...

..The biophysical properties of hyaluronan as well as its ultrastructural organization are analyzed in relation to this proposed function...

..The overall physiological functions of RC-GAP72 are presently unknown, yet our data suggest that RC-GAP72 plays a role in regulating cell morphology and cytoskeletal organization...

..Inducing such changes in the contractility and actin cytoskeleton of HTM cells in glaucomatous eyes in vivo could produce a therapeutically useful increase in outflow facility...

....

..It may promote it through the establishment of exquisitely stereospecific chemical interactions or inhibit it by virtue of steric exclusion and/or electrostatic repulsion...

..We discuss the role of the different network modules in regulating the structural and signalling functions of cell-matrix adhesions...

..Furthermore, we provide evidence in support of multivalent HBV attachment with synergistic interplay. Our data depict a mechanistic view of virus attachment and ingestion...

..5 A resolution at the X11 beamline of DESY and belong to the monoclinic space group P2(1). Crystal unit-cell parameters are estimated to be a = 57, b = 351, c = 70 A, alpha = 90, beta = 113, gamma = 90 degrees...

....

....

..Our findings indicate that B-cell differentiation, as manifested by gene expression profiles, is attenuated by cell adhesion to fibronectin, leading to upregulation of specific genes known to be associated with the pathogenesis of MM...

..These adhesions are highly variable in their morphology, dynamics, and apparent function, yet their molecular diversity is poorly defined...

..Theoretical models have also been used to address the physical mechanisms underlying adhesion-mediated mechanosensing...

..Diverse subpopulations of malignant plasma cells may play distinct roles in the different biological and clinical manifestations of plasma cell dyscrasias, including bone dissemination and selective adhesion to bone marrow compartments...

..Cortactin and p120 are shown to directly interact with each other via the cortactin N-terminal region. We propose that the mechanism underlying p120 functions at the leading edge involves its cooperation with cortactin...

..Thus, allicin is a potent microtubule-disrupting reagent interfering with tubulin polymerization by reaction with tubulin SH groups...

....

..We consider the possibility that in A6 cells single hyaluronan molecules, spanning the whole thickness of the pericellular coat, mediate these tight contacts...

..The significance of combining resolution, throughput and multi-parametric analyses for biomedical research and drug discovery is discussed...

..The outflow-effective concentration of LAT-B administered intracamerally does not significantly affect the corneal endothelium...

....

..Comparison of this pattern with the discrete junctional labeling obtained with the pan-cadherin antibody suggests that different cadherins, co-expressed in the same endothelial cells, may undergo differential surface distribution...

..Disease manifestations of human malignant B-cell variants, isolated based on their differential interactions with fibronectin, were examined in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice...

..We conclude that osteoclasts sense the local properties of the underlying substrate and respond to these signals, both locally and globally...

..This is followed by a protocol for fluorescence resonance energy transfer measurements in live cells...

..Our findings suggest that protein recruitment and growth of focal adhesions are an immediate and direct result of increased contractility induced by microtubule disruption, whereas tyrosine phosphorylation is activated later...

..This study provides a comprehensive information resource on the molecular regulation of multiple cell adhesion features, and sheds light on signaling mechanisms regulating the formation of integrin adhesions...

..The mechanisms whereby the physical properties of the substrate influence osteoclast behavior and their involvement in osteoclast function are discussed...

..Studying the nature of the proteins that undergo de-phosphorylation is critical for the understanding of the mechanisms regulating the processes described above...

..We propose that cadherin-mediated signaling is essential for maintaining viability of confluent endothelial cells, and that its perturbation by N-Ac-CHAVC-NH2 drives these cells to apoptosis...

..Dynamic FRET-based examination indicated that paxillin phosphorylation occurs in specific areas (hotspots) within focal adhesions, whereas FAK phosphorylation is broadly distributed...

..Finally, a quantitative fluorescence microscopic technique using an SH2-containing phosphotyrosine reporter to monitor tyrosine phosphorylation in focal adhesions in live cells is described...

..This suggests that over-expression of the caldesmon gene in the TM may be an effective approach for the gene therapy of glaucoma...

..We define here specific conditions that can lead to the different regimes of FA assembly, including growth, steady state, and disassembly...

..These processes are specific and probably play an important role in EPEC virulence...

..Cellular binding and uptake of extracellular heparanase control its activation, clearance rate and storage within the cells...

..We monitored reduced Rac1-dependent migration also in the cervical cancer cell line SiHa. Therefore we can conclude that up to the stage of tumor formation migratory activity is eliminated...

..Further evidence for a cytoskeletal function of ERD10 was obtained in planta; GFP-ERD10 was able to protect the actin cytoskeleton from latrunculin-mediated disruption in Nicotiana benthamiana leaves...

....

..These findings indicate that a critical RGD density is essential for the establishment of mature and stable integrin adhesions, which, in turn, induce efficient cell spreading and formation of focal adhesions...

..We propose here a molecular model for the tyrosine phosphorylation-dependent regulation of focal adhesion kinase organization involving Src kinases and an inhibitory phosphorylation of the C-terminal (Tyr-925) tyrosine residue...

..Detailed consideration is also given to the fact that protein clusters such as those found at focal adhesion sites represent, to a large extent, hierarchically organized cooperativity among various proteins...

..Supramolecular design of artificial bioactive extracellular matrices to tune cell response may prove to be a powerful strategy in regenerative medicine and to study biological processes...

..Here, we propose that microtubules determine cell polarity by modulating the pattern of adhesions that a cell develops with the underlying matrix, through focal inhibitions of contractility...

..We propose that differential positional clustering of the integrin transmembrane receptors is used by cells for exploring and interpreting their environment, at high spatial sensitivity...