title: Lulu2 regulates the circumferential actomyosin tensile system in epithelial cells through p114RhoGEF.
abstract: Myosin II-driven mechanical forces control epithelial cell shape and morphogenesis. In particular, the circumferential actomyosin belt, which is located along apical cell-cell junctions, regulates many cellular processes. Despite its importance, the molecular mechanisms regulating the belt are not fully understood. In this paper, we characterize Lulu2, a FERM (4.1 protein, ezrin, radixin, moesin) domain-containing molecule homologous to Drosophila melanogaster Yurt, as an important regulator. In epithelial cells, Lulu2 is localized along apical cell-cell boundaries, and Lulu2 depletion by ribonucleic acid interference results in disorganization of the circumferential actomyosin belt. In its regulation of the belt, Lulu2 interacts with and activates p114RhoGEF, a Rho-specific guanine nucleotide exchanging factor (GEF), at apical cell-cell junctions. This interaction is negatively regulated via phosphorylation events in the FERM-adjacent domain of Lulu2 catalyzed by atypical protein kinase C. We further found that Patj, an apical cell polarity regulator, recruits p114RhoGEF to apical cell-cell boundaries via PDZ (PSD-95/Dlg/ZO-1) domain-mediated interaction. These findings therefore reveal a novel molecular system regulating the circumferential actomyosin belt in epithelial cells.
authors: Global Centers of Excellence Program for Integrative Membrane Biology, Graduate School of Medicine, Kobe University, Chuo-ku, Kobe 650-0017, Japan.
authors: Hiroyuki
authors: H
authors: Nakajima
authors: Takuji
authors: T
authors: Tanoue
mesh_terms: D000205:Actomyosin / Q000502:physiology*; D000818:Animals; D016764:Cell Polarity; D048430:Cell Shape; D003598:Cytoskeletal Proteins / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D051379:Mice; D021381:Protein Transport; D064067:Rho Guanine Nucleotide Exchange Factors
chemical_list: C577230:ARHGEF18 protein, human; D003598:Cytoskeletal Proteins; D020662:Guanine Nucleotide Exchange Factors; C569630:LULU2 protein, mouse; D064067:Rho Guanine Nucleotide Exchange Factors; D000205:Actomyosin