Moesin and myosin phosphatase confine neutrophil orientation in a chemotactic gradient.
Bottom Line: Neutrophils respond to invading bacteria by adopting a polarized morphology, migrating in the correct direction, and engulfing the bacteria.Attractant-induced activation of myosin phosphatase deactivated moesin at the prospective leading edge to break symmetry and establish polarity.Subsequent translocation of moesin to the trailing edge confined the formation of a prominent pseudopod directed toward pathogens and prevented secondary pseudopod formation in other directions.
Affiliation: Department of Pharmacology and Department of Medicine, University of Illinois, Chicago, IL 60612.Show MeSH
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Mentions: When control cells were exposed to an fMLF gradient, they migrated up the entire gradient (Fig. 9 A). PP1c RNAi–treated cells also migrated, but with poor directionality (Fig. 9 A), and the CI was significantly lower in PP1 RNAi–treated cells compared with controls (0.26 vs. 0.72, P < 0.01; Fig. 9 B). The migration speed of PP1c RNAi–treated cells was also significantly decreased (11.5 vs. 18.4 µm/min, P < 0.01; Fig. 9 C). Similar results were obtained in MBS RNAi cells (Fig. 9, A–C). Expression of the moesin-T558A mutant, but not WT moesin, partially restored cell migration in PP1c RNAi cells (Fig. 9, D and E). Collectively, our data indicate that inhibition of myosin phosphatase prevented moesin dephosphorylation and dissociation from cell membrane, thus causing unstable cell polarity and impaired cell migration.
Affiliation: Department of Pharmacology and Department of Medicine, University of Illinois, Chicago, IL 60612.