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: Moesin inactivates both frontness and backness signals in resting neutrophils through the inhibition of Rho GTPases, as described above. Hence, to undergo polarization and migration, cells must deactivate moesin-mediated inhibition and thereby initiate cell migration. We next addressed the mechanism responsible for breaking the symmetry and initiating cell migration. We focused on the role of myosin phosphatase, which dephosphorylates both moesin and MLC (Fukata et al., 1998). Both the catalytic subunit (PP1c) and the MBS of myosin phosphatase are coimmunoprecipitated with the Hem-1 complex, which organizes the neutrophil’s leading edge (Weiner et al., 2006). We first confirmed PP1c localization to the leading edge by expressing YFP-tagged PP1c in HL60 cells. PP1c-YFP localized to both the cytosol and the nucleus in the basal stage. A uniform concentration of fMLF (100 nM) induced the recruitment of PP1c-YFP to the cell periphery and subsequently to the leading edge in polarized cells (Fig. 8 A; a time course of PP1 localization is shown in Table S2).
Affiliation: Department of Pharmacology and Department of Medicine, University of Illinois, Chicago, IL 60612.