title: Roles of p-ERM and Rho-ROCK signaling in lymphocyte polarity and uropod formation.
abstract: Front-rear asymmetry in motile cells is crucial for efficient directional movement. The uropod in migrating lymphocytes is a posterior protrusion in which several proteins, including CD44 and ezrin/radixin/moesin (ERM), are concentrated. In EL4.G8 T-lymphoma cells, Thr567 phosphorylation in the COOH-terminal domain of ezrin regulates the selective localization of ezrin in the uropod. Overexpression of the phosphorylation-mimetic T567D ezrin enhances uropod size and cell migration. T567D ezrin also induces construction of the CD44-associated polar cap, which covers the posterior cytoplasm in staurosporine-treated, uropod-disrupted EL4.G8 cells or in naturally unpolarized X63.653 myeloma cells in an actin cytoskeleton-dependent manner. Rho-associated coiled coil-containing protein kinase (ROCK) inhibitor Y-27632 disrupts the uropod but not the polar cap, indicating that Rho-ROCK signaling is required for posterior protrusion but not for ERM phosphorylation. Phosphorylated ezrin associates with Dbl through its NH2-terminal domain and causes Rho activation. Moreover, constitutively active Q63L RhoA is selectively localized in the rear part of the cells. Thus, phosphorylated ERM has a potential function in establishing plasma membrane "posteriority" in the induction of the uropod in T lymphocytes.
authors.affiliation: Center for Molecular Biology and Genetics, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Tomoya
authors.initials: T
authors.lastname: Katakai
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gonda
authors.forename: Manabu
authors.initials: M
authors.lastname: Sugai
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
mesh_terms: D000199:Actins / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D002633:Chemotaxis; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000378:metabolism; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins; D008214:Lymphocytes / Q000378:metabolism*; D016399:Lymphoma, T-Cell / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000099149:Ezrin
chemical_list: D000199:Actins; D000577:Amides; D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D049452:Green Fluorescent Proteins; D020662:Guanine Nucleotide Exchange Factors; D018960:Hyaluronan Receptors; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011725:Pyridines; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D000099149:Ezrin; C108830:Y 27632; C071058:moesin; C071776:radixin