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Vol. 12, Issue 9, 2742-2755, September 2001

Myosin Va Bound to Phagosomes Binds to F-Actin and Delays Microtubule-dependent Motility

Ahmed Al-Haddad,^* Marion A. Shonn,^* Bärbel Redlich,^* Ariel Blocker,^§ Janis K. Burkhardt, Hanry Yu,^¶# John A. Hammer III,^@ Dieter G. Weiss,^* Walter Steffen,^** Gareth Griffiths, and Sergei A. Kuznetsov^*

 ^*Institut für Zellbiologie und Biosystemtechnik, FB Biowissenschaften, Universität Rostock, D-18051 Rostock, Germany;  European Molecular Biology Laboratory, Heidelberg, Germany;  ^¶National University Medical Institute, Clinical Research Centre, Singapore 117597, Republic of Singapore; and  ^@Laboratory of Cell Biology, National Institutes of Health, Bethesda, Maryland 20892

We established a light microscopy-based assay that reconstitutes the binding of phagosomes purified from mouse macrophages to preassembled F-actin in vitro. Both endogenous myosin Va from mouse macrophages and exogenous myosin Va from chicken brain stimulated the phagosome-F-actin interaction. Myosin Va association with phagosomes correlated with their ability to bind F-actin in an ATP-regulated manner and antibodies to myosin Va specifically blocked the ATP-sensitive phagosome binding to F-actin. The uptake and retrograde transport of phagosomes from the periphery to the center of cells in bone marrow macrophages was observed in both normal mice and mice homozygous for the dilute-lethal spontaneous mutation (myosin Va null). However, in dilute-lethal macrophages the accumulation of phagosomes in the perinuclear region occurred twofold faster than in normal macrophages. Motion analysis revealed saltatory phagosome movement with temporarily reversed direction in normal macrophages, whereas almost no reversals in direction were observed in dilute-lethal macrophages. These observations demonstrate that myosin Va mediates phagosome binding to F-actin, resulting in a delay in microtubule-dependent retrograde phagosome movement toward the cell center. We propose an "antagonistic/cooperative mechanism" to explain the saltatory phagosome movement toward the cell center in normal macrophages.

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Present address: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138; ^§Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK; Department of Pathology, MC1089 the University of Chicago, Chicago, IL 60637; ^#National University Medical Institute, Blk.MD11 03-02, Clinical Research Centre, 10 Medical Dr., Singapore 117597; ^**GKT School of Biomedical Sciences, MRC Muscle and Cell, London SE1 1UL, UK.

Corresponding author. E-mail address: sergei.kuznetsov{at}biologie.uni-rostock.de.

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Molecular Biology of the Cell
Vol. 12, 2742-2755, September 2001
Copyright © 2001 by The American Society for Cell Biology

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