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Appears in Collections:Biological and Environmental Sciences Journal Articles
Peer Review Status: Refereed
Title: Two distinct cytoplasmic regions of the beta2 integrin chain regulate RhoA function during phagocytosis
Author(s): Wiedemann, Agnes
Patel, Jayesh C
Lim, Jenson
Tsun, Andy
van Kooyk, Yvette
Caron, Emmanuelle
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Issue Date: 27-Mar-2006
Date Deposited: 16-Sep-2014
Citation: Wiedemann A, Patel JC, Lim J, Tsun A, van Kooyk Y & Caron E (2006) Two distinct cytoplasmic regions of the beta2 integrin chain regulate RhoA function during phagocytosis. Journal of Cell Biology, 172 (7), pp. 1069-1079.
Abstract: AlphaMbeta2 integrins mediate phagocytosis of opsonized particles in a process controlled by RhoA, Rho kinase, myosin II, Arp2/3, and actin polymerization. AlphaMbeta2, Rho, Arp2/3, and F-actin accumulate underneath bound particles; however, the mechanism regulating Rho function during alphaMbeta2-mediated phagocytosis is poorly understood. We report that the binding of C3bi-opsonized sheep red blood cells (RBCs) to alphaMbeta2 increases Rho-GTP, but not Rac-GTP, levels. Deletion of the cytoplasmic domain of beta2, but not of alphaM, abolished Rho recruitment and activation, as well as phagocytic uptake. Interestingly, a 16-amino acid (aa) region in the membrane-proximal half of the beta2 cytoplasmic domain was necessary for activating Rho. Three COOH-terminal residues (aa 758-760) were essential for beta2-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.
DOI Link: 10.1083/jcb.200508075
Rights: Ownership of copyright remains with RUP authors, who may reuse their own material forany purpose, including commercial profit, as long as they provide proper attribution. ¬©Wiedemann et al., 2006. Originally published in Journal of Cell Biology. doi: 10.1083/jcb.200508075

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