title: Hippo kinases maintain polarity during directional cell migration in Caenorhabditis elegans.
abstract: Precise positioning of cells is crucial for metazoan development. Despite immense progress in the elucidation of the attractive cues of cell migration, the repulsive mechanisms that prevent the formation of secondary leading edges remain less investigated. Here, we demonstrate that Caenorhabditis elegans Hippo kinases promote cell migration along the anterior-posterior body axis via the inhibition of dorsal-ventral (DV) migration. Ectopic DV polarization was also demonstrated in gain-of-function mutant animals for C. elegans RhoG MIG-2. We identified serine 139 of MIG-2 as a novel conserved Hippo kinase phosphorylation site and demonstrated that purified Hippo kinases directly phosphorylate MIG-2S139Live imaging analysis of genome-edited animals indicates that MIG-2S139phosphorylation impedes actin assembly in migrating cells. Intriguingly, Hippo kinases are excluded from the leading edge in wild-type cells, while MIG-2 loss induces uniform distribution of Hippo kinases. We provide evidence that Hippo kinases inhibit RhoG activity locally and are in turn restricted to the cell body by RhoG-mediated polarization. Therefore, we propose that the Hippo-RhoG feedback regulation maintains cell polarity during directional cell motility.
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing, China.
authors.forename: Guoxin
authors.identifier: 0000-0002-6754-936X
authors.initials: G
authors.lastname: Feng
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing, China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: National Institute of Biological Science, Beijing, China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Li
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing, China.
authors.forename: Qirong
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Chai
authors.affiliation: National Institute of Biological Science, Beijing, China.
authors.forename: Meng-Qiu
authors.initials: MQ
authors.lastname: Dong
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing, China guangshuoou@tsinghua.edu.cn.
authors.forename: Guangshuo
authors.identifier: 0000-0003-1512-7824
authors.initials: G
authors.lastname: Ou
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002465:Cell Movement; D016764:Cell Polarity; D025461:Feedback, Physiological; D010766:Phosphorylation; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D029742:Caenorhabditis elegans Proteins; D017346:Protein Serine-Threonine Kinases; C442327:Mig-2 protein, C elegans; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins
keywords: Hippo kinase; RhoG; cell migration; cell polarity