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J. Biol. Chem., Vol. 277, Issue 36, 32963-32969, September 6, 2002

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Dynamitin Controls ₂ Integrin Avidity by Modulating Cytoskeletal Constraint on Integrin Molecules^*

Tianquan Jin and Jianxun Li

From the Department of Oral Biology, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois 60612

Dynamitin, a subunit of the microtubule-dependent motor complex, was implicated in cell adhesion by binding to MacMARCKS (Macrophage-enriched myristoylated alanine-rice C kinase substrate). However, how dynamitin is involved in cell adhesion is unclear despite the fact that both MacMARCKS and microtubules regulate ₂ integrin activation. We report that dynamitin regulates ₂ integrin avidity toward iC3b by modulating the lateral mobility of ₂ integrin molecules. Using the single particle tracking method, we found that integrin molecular mobility in cells expressing the fusion protein CFP (cyan fluorescent protein)-dynamitin or CFP-MB (the MacMARCKS binding domain peptide of dynamitin) increased 6-fold over the control cells, suggesting that disturbing dynamitin function dramatically altered the cytoskeletal constraint on ₂ integrin molecules. Further mechanistic studies revealed that overexpression of dynamitin stimulated the phosphorylation of endogenous MacMARCKS protein, which lead to the enhanced tyrosine phosphorylation of paxillin. This effect of dynamitin correlates with the observation that higher concentration of PKC inhibitor is required to block ₂ integrin mobility in dynamitin-expressing cells. Although dynamitin acts at the point of MacMARCKS phosphorylation, it is upstream of RhoA, because its effect was blocked by RhoA inhibitor. Thus, we conclude that dynamitin is a part of the cytoskeletal constraint that locks ₂ integrin in the inactive form.

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