title: Regulation of the MEX-5 gradient by a spatially segregated kinase/phosphatase cycle.
abstract: Protein concentration gradients encode spatial information across cells and tissues and often depend on spatially localized protein synthesis. Here, we report that a different mechanism underlies the MEX-5 gradient. MEX-5 is an RNA-binding protein that becomes distributed in a cytoplasmic gradient along the anterior-to-posterior axis of the one-cell C. elegans embryo. We demonstrate that the MEX-5 gradient is a direct consequence of an underlying gradient in MEX-5 diffusivity. The MEX-5 diffusion gradient arises when the PAR-1 kinase stimulates the release of MEX-5 from slow-diffusive, RNA-containing complexes in the posterior cytoplasm. PAR-1 directly phosphorylates MEX-5 and is antagonized by the spatially uniform phosphatase PP2A. Mathematical modeling and in vivo observations demonstrate that spatially segregated phosphorylation and dephosphorylation reactions are sufficient to generate stable protein concentration gradients in the cytoplasm. The principles demonstrated here apply to any spatially segregated modification cycle that affects protein diffusion and do not require protein synthesis or degradation.
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Center for Cell Dynamics, Johns Hopkins School of Medicine, 725 N. Wolfe Street, PCTB 706, Baltimore, MD 21205, USA.
authors.forename: Erik E
authors.initials: EE
authors.lastname: Griffin
authors.forename: David J
authors.initials: DJ
authors.lastname: Odde
authors.forename: Geraldine
authors.initials: G
authors.lastname: Seydoux
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004058:Diffusion; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D015053:Zygote / Q000737:chemistry / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C410587:MEX-5 protein, C elegans; D016601:RNA-Binding Proteins; D012313:RNA; C409406:PAR-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D054648:Protein Phosphatase 2