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Roles of p-ERM and Rho-ROCK signaling in lymphocyte polarity and uropod formation.

Lee JH, Katakai T, Hara T, Gonda H, Sugai M, Shimizu A - J. Cell Biol. (2004)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Molecular Biology and Genetics, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.

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.

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Model of lymphocyte polarization and uropod formation. During the construction of the motile polarized morphology in lymphocytes in response to chemoattraction or adhesion signals (directional cues), two codependent steps are proposed: “posteriorization” of the plasma membrane mediated by ERM phosphorylation, and “uropod protrusion” mediated by Rho–ROCK activation.
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fig8: Model of lymphocyte polarization and uropod formation. During the construction of the motile polarized morphology in lymphocytes in response to chemoattraction or adhesion signals (directional cues), two codependent steps are proposed: “posteriorization” of the plasma membrane mediated by ERM phosphorylation, and “uropod protrusion” mediated by Rho–ROCK activation.

Mentions: The triggering of lymphocyte migration by various attractants involves complicated signaling (Ward et al., 1998; Hogg et al., 2003), although the overall picture of it remains incomplete. Environmental directional cues are thought to trigger the sequential signaling events upstream of the ERM phosphorylation, as well as the Rho–ROCK pathway, in unpolarized lymphocytes, and to induce the polarized morphology of lymphocytes that are able to migrate efficiently (Fig. 8). Our observations suggest that this process can be dissected into two steps: p-ERM–mediated plasma membrane polarization and Rho–ROCK-mediated uropod protrusion (Fig. 8). In future studies, it will be important to identify any kinases that phosphorylate ERM CT Thr residues, to link the upstream signaling with p-ERM during lymphocyte migration.


Roles of p-ERM and Rho-ROCK signaling in lymphocyte polarity and uropod formation.

Lee JH, Katakai T, Hara T, Gonda H, Sugai M, Shimizu A - J. Cell Biol. (2004)

Model of lymphocyte polarization and uropod formation. During the construction of the motile polarized morphology in lymphocytes in response to chemoattraction or adhesion signals (directional cues), two codependent steps are proposed: “posteriorization” of the plasma membrane mediated by ERM phosphorylation, and “uropod protrusion” mediated by Rho–ROCK activation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172551&req=5

fig8: Model of lymphocyte polarization and uropod formation. During the construction of the motile polarized morphology in lymphocytes in response to chemoattraction or adhesion signals (directional cues), two codependent steps are proposed: “posteriorization” of the plasma membrane mediated by ERM phosphorylation, and “uropod protrusion” mediated by Rho–ROCK activation.
Mentions: The triggering of lymphocyte migration by various attractants involves complicated signaling (Ward et al., 1998; Hogg et al., 2003), although the overall picture of it remains incomplete. Environmental directional cues are thought to trigger the sequential signaling events upstream of the ERM phosphorylation, as well as the Rho–ROCK pathway, in unpolarized lymphocytes, and to induce the polarized morphology of lymphocytes that are able to migrate efficiently (Fig. 8). Our observations suggest that this process can be dissected into two steps: p-ERM–mediated plasma membrane polarization and Rho–ROCK-mediated uropod protrusion (Fig. 8). In future studies, it will be important to identify any kinases that phosphorylate ERM CT Thr residues, to link the upstream signaling with p-ERM during lymphocyte migration.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Molecular Biology and Genetics, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.

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.

Show MeSH
Related in: MedlinePlus