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Cells explore their environment by sending out filopodia and lamellipodia. These protrusions encounter extracellular matrix components that encourage adhesion and cell spreading through actin polymerization. On page 881, DeMali et al. show how sites of cell adhesion specifically attract actin-polymerizing proteins, thus linking adhesion to protrusion.( I0 Z% g# T. t6 l9 t7 a
3 W; @0 l2 K* M+ C) i7 [" Z. zAdhesion and actin polymerization are coordinated by an interaction between proteins essential for both. DeMali et al. identified an association between vinculin, a protein found in focal complexes, and the Arp2/3 actin nucleation and remodeling complex. Induction of lamellipodial formation (e.g., by EGF) or integrin clustering (e.g., by fibronectin) stimulated the binding of vinculin to Arp2/3. The strongest association required signaling effects downstream of PI3K, including Rac1-induced activation of Arp2/3 and a PIP2-induced conformational change in vinculin.
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Binding recruited Arp2/3 to focal complexes at the leading edge of migrating cells. This recruitment might ensure that components of the focal complex are hooked to the cytoskeleton, which should help in the maturation of focal complexes into focal adhesions. Cell spreading and lamellipodial formation were diminished in cells that expressed a mutant version of vinculin that does not bind to Arp2/3.
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The Arp2/3 complex was not found in mature adhesions, where the actin linkages were fully formed. The Arp2/3 complex binding site on vinculin is in a region used by several other proteins, including VASP, that might displace Arp2/3 in mature adhesions. The transient nature of the Arp2/3 association with vinculin should help concentrate new actin polymerization only at the newest adhesions, and might explain why the interaction had not been detected previously.(Arp2/3 (white, left) is brought to vincu) |
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发表于 2009-3-6 00:18
发表于 2015-5-22 16:18
