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Regulation of protrusive and contractile cell-matrix contacts

MRC Laboratory for Molecular Cell Biology and Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK

View larger version (26K): [in a new window]   Fig. 1. (A) Schematic view of the general structural components of a functional matrix contact. (1) ECM ligands, (2) specific matrix adhesion receptors, (3) linker complex and (4) cytoskeletal connection. (B) Major functional categories of matrix contacts and their sites of formation are listed.

View larger version (145K): [in a new window]   Fig. 2. Examples of cellular coordination of matrix contacts. Scanning EM views (A-C,J,K) or differential interference contrast microscopy (D-H) of human diploid WI-38 fiboblasts (A-C), MRC-5 cells from human fetal lung (D-H), Balb/c 3T3 mouse fibroblasts (J,K) or syndecan-1 transfected COS-7 green monkey kidney cells (L) are shown. They are taken at different times of adhesion to glass in the presence of serum vitronectin (A-H) or 2 hours adhesion to fibronectin (J), 2 hours adhesion to platelet factor 4 (K) or 1 hour in the presence of thrombospondin-1 (L). Initial matrix contact by filopodia and spikes (A,D) is followed by extension of lamellipodia (B,E) accompanied by membrane ruffling until full spreading is reached (C,F). Formation of contractile contacts produces alterations in cell shape (G) that are reversed with the long-term development of matrix assembly sites and fibrillar matrix (H). Under conditions of high adhesion, retraction fibres are often associated with contractile contacts (J). (K,L). In glycosaminoglycan/proteoglycan-mediated adhesion, filopodia, spikes and lamellipodia are the predominant contacts. (L) A cell stained with TRITC-phalloidin. Bar in J, 4 µm; K,L, 5 µm. Panels A-C reproduced from Rajaraman et al (Rajaraman et al., 1974), D-H from Witkowski and Brighton (Witkowski and Brighton, 1971), J,K from Laterra et al. (Laterra et al., 1983) with permission of Academic Press.

View larger version (51K): [in a new window]   Fig. 3. Mechanisms of matrix contact assembly and remodelling (A) in a podosome and (B) in a focal adhesion. The inset in B shows the positive and negative actions of protein complexes formed on paxillin subsequent to phosphorylation of residues Y31 and Y118 by focal adhesion kinase. The green circle and yellow oblong represent proximal components of the focal adhesion linker complex such as talin and filamin. Asterisks indicate activated forms of c-Src, Pyk2 and Pak.

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