RRC ID 53386
Author Feng G, Zhu Z, Li WJ, Lin Q, Chai Y, Dong MQ, Ou G.
Title Hippo kinases maintain polarity during directional cell migration in Caenorhabditis elegans.
Journal EMBO J
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-2S139 Live imaging analysis of genome-edited animals indicates that MIG-2S139 phosphorylation 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.
Volume 36(3)
Pages 334-345
Published 2017-2-1
DOI 10.15252/embj.201695734
PII embj.201695734
PMID 28011581
PMC PMC5286363
MeSH Actins / metabolism Animals Caenorhabditis elegans / enzymology* Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism Cell Movement* Cell Polarity* Feedback, Physiological Phosphorylation Protein Multimerization Protein Processing, Post-Translational Protein-Serine-Threonine Kinases / metabolism* rac GTP-Binding Proteins / metabolism rho GTP-Binding Proteins / metabolism*
IF 11.227
Times Cited 8
C.elegans tm1900 tm4081 tm1416