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Two Distinct Cytoplasmic Regions of the β2Integrin Chain Regulate RhoA Function during Phagocytosis

$\alpha M\beta_2$integrins mediate phagocytosis of opsonized particles in a process controlled by RhoA, Rho kinase, myosin II, Arp2/3, and actin polymerization.$\alpha M\beta_2$Rho, Arp2/3, and F-actin accumulate underneath bound particles; however, the mechanism regulating Rho function during$\beta...

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Published in:The Journal of cell biology 2006-03, Vol.172 (7), p.1069-1079
Main Authors: Agnès Wiedemann, Jayesh C. Patel, Jenson Lim, Andy Tsun, van Kooyk, Yvette, Caron, Emmanuelle
Format: Article
Language:English
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Summary:$\alpha M\beta_2$integrins mediate phagocytosis of opsonized particles in a process controlled by RhoA, Rho kinase, myosin II, Arp2/3, and actin polymerization.$\alpha M\beta_2$Rho, Arp2/3, and F-actin accumulate underneath bound particles; however, the mechanism regulating Rho function during$\beta M\beta_2-mediated$phagocytosis is poorly understood. We report that the binding of C3bi-opsonized sheep red blood cells (RBCs) to$\alpha M\beta_2$increases Rho-GTP, but not Rac-GTP, levels. Deletion of the cytoplasmic domain of β2, but not of αM, abolished Rho recruitment and activation, as well as phagocytic uptake. Interestingly, a 16-amino acid (aa) region in the membrane-proximal half of the β2cytoplasmic domain was necessary for acti vating Rho. Three COOH-terminal residues (aa 758-760) were essential for$\beta_2-induced$accumulation of Rho at complement receptor 3 (CR3) phagosomes. Activation of Rho was necessary, but not sufficient, for its stable recruitment underneath bound particles or for uptake. However, recruitment of active Rho was sufficient for phagocytosis. Our data shed light on the mechanism of outside-in signaling, from ligated integrins to the activation of Rho GTPase signaling.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200508075