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First published online 20 November 2002
doi: 10.1242/jcs.00235

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Phosphoinositide-3-kinase-independent contractile activities associated with Fc-receptor-mediated phagocytosis and macropinocytosis in macrophages

¹ Department of Histology and Cell Biology, Kagawa Medical University, Miki, Kagawa 761-0793, Japan
² Department of Biochemistry, Kagawa Medical University, Miki, Kagawa 761-0793, Japan
³ Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA

^* Author for correspondence (e-mail: naraki{at}kms.ac.jp)

Accepted 23 October 2002

Previous studies have shown that Fc receptor (FcR)-mediated phagocytosis and macropinocytosis in macrophages consist of two dissociable activities: a phosphoinositide 3-kinase (PI3K)-independent extension of phagocytic cups and a PI3K-dependent contractile mechanism that closes phagosomes and ruffles into intracellular organelles. Here, we identify an additional contractile activity that persists in the presence of the PI3K inhibitor wortmannin. ML-7, an inhibitor of myosin-light-chain kinase (MLCK), inhibited FcR-mediated phagocytosis, macropinocytosis and cell movements associated with ruffling. Scanning electron microscopy demonstrated a striking difference in morphology between phagocytic cups in the different inhibitors: whereas phagocytic cups of control cells and wortmannin-treated cells conformed closely to particles and appeared to have constricted them, the phagocytic cups in cells treated with ML-7 were more open. Video microscopy of macrophages expressing green-fluorescent-protein (GFP)—actin fusions revealed that bound IgG-opsonized erythrocytes were squeezed during phagosome formation and closure. In ML-7, GFP—actin-rich protrusions extended outward but failed to squeeze particles. Moreover, in contrast to the effects of PI3K inhibitors, ML-7 markedly reduced ruffle movement, and perturbed circular ruffle formation. These PI3K-independent myosin-II-based contractile activities that squeeze phagocytic cups and curve ruffles therefore represent a third component activity of the actin cytoskeleton during phagocytosis and macropinocytosis.

Key words: Myosin, Myosin light chain kinase, Actin, Phosphoinositide 3-kinase, Phagocytosis, Macropinocytosis

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