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- Title
Roles of p-ERM and Rho-ROCK signaling in lymphocyte polarity and uropod formation.
- Authors
Jong-Hwan Lee; Katakai, Tomoya; Hara, Takahiro; Gonda, Hiroyuki; Sugai, Manabu; Shimizu, Akira
- 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 DbI through its NH2-terminal domain and causes Rho activation. Moreover, consecutively 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.
- Subjects
LYMPHOCYTES; UROPODA; LEUCOCYTES; CELL migration; CELL membranes; PROTEIN kinases
- Publication
Journal of Cell Biology, 2004, Vol 167, Issue 2, p327
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200403091