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Integrin-mediated adhesions are highly complex structures, consisting of multiple extracellular and cellular components, and associated with the actin cytoskeleton (Fig. 1, top and center panels). Based on their molecular composition and morphology, these adhesions fall into several categories, namely focal adhesions, focal complexes, fibrillar adhesions and podosomes. To determine the roles of individual components, Sabina Winograd-Katz is knocking-down individual proteins, using a siRNA transfection approach, and is determining the consequent effects of this treatment on adhesion site development and dynamics. Tova Volberg is mapping different states of integrins in stressed and relaxed adhesions, using conformationspecific antibodies, and Ronen Zaidel-Bar explores the phosphorylation of specific focal adhesion molecules (e.g. paxillin) and determines the involvement of this modification in regulating adhesion formation. A particular form of integrin-mediated adhesions, namely podosomes, found in osteoclasts and macrophages are investigated by Chen Luxenburg (in collaboration with Lia Addadi). These, dot-like adhesions were shown to undergo transformation from single contacts to large “sealing zone-like structures” that participate in bone resorption. This process is tightly regulated by the cytoplasmic kinase src, whose target, cortactin, regulates actin dynamics in the adhesion site (Fig 1, middle panel, Right image). The role of cortactin in cell protrusion, as well as in cell-to-cell adhesion, is further investigated by Elad Landoy (in collaboration with A. Bershadsky), focusing on different molecular partners, as well as modulators of this protein.
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Fig. 1 Diversity of integrin adhesions. Top panel –Porcine aortic endothelial cells, double-labeled for actin (green) and phospho-tyrosine (red). Notice focal complexes at the cell edge and focal adhesions at the ends of actin cables. Middle panel- Left: A scheme showing the molecular complexity of integrin adhesions (Nature Reviews, Molecular Cell Biology 2:793-805 (2001)); Right: Ratio image of an osteoclast, labeled for actin (blue) and vinculin (red). Overlaps between the two are represented by a spectral scale. Bottom panel- Porcine aortic endothelial cells, double labeled for paxillin (green) and phosphopaxillin (red). Notice the exclusion of the phosphorylated form from fibrillar adhesions (arrowheads). |
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