title: Moesin and myosin phosphatase confine neutrophil orientation in a chemotactic gradient.
abstract: Neutrophils respond to invading bacteria by adopting a polarized morphology, migrating in the correct direction, and engulfing the bacteria. How neutrophils establish and precisely orient this polarity toward pathogens remains unclear. Here we report that in resting neutrophils, the ERM (ezrin, radixin, and moesin) protein moesin in its active form (phosphorylated and membrane bound) prevented cell polarization by inhibiting the small GTPases Rac, Rho, and Cdc42. 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. Therefore, both moesin-mediated inhibition and its localized deactivation by myosin phosphatase are essential for neutrophil polarization and effective neutrophil tracking of pathogens.
authors.affiliation: Department of Pharmacology and Department of Medicine, University of Illinois, Chicago, IL 60612.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Laboratory of Biological Science and Laboratory of Cellular Dynamics, Graduate School of Medicine, Osaka University, Suita 565-0871, Osaka, Japan.
authors.forename: Koya
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Laboratory of Biological Science and Laboratory of Cellular Dynamics, Graduate School of Medicine, Osaka University, Suita 565-0871, Osaka, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tsukita
authors.affiliation: Laboratory of Biological Science and Laboratory of Cellular Dynamics, Graduate School of Medicine, Osaka University, Suita 565-0871, Osaka, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Ishii
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology and Department of Medicine, University of Illinois, Chicago, IL 60612.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Department of Medicine, University of Illinois, Chicago, IL 60612.
authors.forename: Luyang
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Pharmacology and Department of Medicine, University of Illinois, Chicago, IL 60612.
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.affiliation: Department of Pharmacology and Department of Medicine, University of Illinois, Chicago, IL 60612.
authors.forename: Shalina
authors.initials: S
authors.lastname: Taylor
authors.affiliation: Department of Pharmacology and Department of Medicine, University of Illinois, Chicago, IL 60612.
authors.forename: Myung-Jin
authors.initials: MJ
authors.lastname: Oh
authors.affiliation: Department of Pharmacology and Department of Medicine, University of Illinois, Chicago, IL 60612.
authors.forename: Irena
authors.initials: I
authors.lastname: Levitan
authors.affiliation: Department of Pharmacology and Department of Medicine, University of Illinois, Chicago, IL 60612.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Ye
authors.affiliation: Department of Pharmacology and Department of Medicine, University of Illinois, Chicago, IL 60612.
authors.forename: Graeme K
authors.initials: GK
authors.lastname: Carnegie
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China jingsong@uic.edu zhaoy@ioz.ac.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology and Department of Medicine, University of Illinois, Chicago, IL 60612.
authors.forename: Asrar B
authors.initials: AB
authors.lastname: Malik
authors.affiliation: Department of Pharmacology and Department of Medicine, University of Illinois, Chicago, IL 60612 jingsong@uic.edu zhaoy@ioz.ac.cn.
authors.forename: Jingsong
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D002460:Cell Line; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D017353:Gene Deletion; D055785:Gene Knockdown Techniques; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D043263:Myosin-Light-Chain Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D010766:Phosphorylation; D011485:Protein Binding; D034622:RNA Interference; D064067:Rho Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D008840:Microfilament Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; C071058:moesin; D043263:Myosin-Light-Chain Phosphatase; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins