Regulation of the MEX-5 gradient by a spatially segregated kinase/phosphatase cycle

Erik E. Griffin, David J. Odde, Geraldine Seydoux

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82 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)955-968
Number of pages14
JournalCell
Volume146
Issue number6
DOIs
StatePublished - Sep 16 2011

Bibliographical note

Funding Information:
We thank F. Motegi for providing the Dendra2 construct, S. He for help with sucrose gradients, and N. Perkins and E. Pryce at the JHU Integrated Imaging Center for assistance with FCS. We thank K. Kemphues for providing strains and antibodies. We thank A. Cuenca for generation of the GFP::PAR-1 transgenic strain. We thank S. Kuo for helpful conversations and members of the Seydoux lab for helpful comments on the manuscript. This work was supported by the National Institutes of Health (Grants R01HD37047 [G.S.] and R01 GM71522 [D.J.O.]) and the American Cancer Society (Grant PF-08-158-01-DDC [E.E.G.]). G.S. is an Investigator of the Howard Hughes Medical Institute.

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