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

Cell. 2011 Sep 16;146(6):955-68. doi: 10.1016/j.cell.2011.08.012.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / chemistry
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism*
  • Cytoplasm / metabolism
  • Diffusion
  • Phosphorylation
  • Protein Phosphatase 2 / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA / metabolism
  • RNA-Binding Proteins / metabolism
  • Zygote / chemistry
  • Zygote / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • MEX-5 protein, C elegans
  • RNA-Binding Proteins
  • RNA
  • PAR-1 protein, C elegans
  • Protein-Serine-Threonine Kinases
  • Protein Phosphatase 2