Modeling protein dynamics in Caenorhabditis elegans embryos reveals that the PLK-1 gradient relies on weakly coupled reaction–diffusion mechanisms

Abstract

Significance Intracellular gradients have essential roles in cell and developmental biology, but their formation is not fully understood. We have developed a computational approach facilitating interpretation of protein dynamics and gradient formation. We have combined this computational approach with experiments to understand how Polo-Like Kinase 1 (PLK-1) forms a cytoplasmic gradient in Caenorhabditis elegans embryos. Although the PLK-1 gradient depends on the Muscle EXcess-5/6 (MEX-5/6) proteins, we reveal differences in PLK-1 and MEX-5 gradient formation that can be explained by a model with two components, PLK-1 bound to MEX-5 and unbound PLK-1. Our combined approach suggests that a weak coupling between PLK-1 and MEX-5 reaction–diffusion mechanisms dictates the dynamic exchange of PLK-1 with the cytoplasm, explaining PLK-1 high diffusivity and smooth gradient.

PLK-1 regulates MEX-1 polarization in theC. eleganszygote

“…The interaction between MEX-5/6 and PLK-1 kinase leads to the enrichment of PLK-1 in the anterior cytoplasm of the polarized zygote (Barbieri et al, 2022;Nishi et al, 2008). To test whether the interaction between MEX-5 and PLK-1 is required for MEX-1 segregation, we analyzed MEX-1::GFP dynamics in mex-5(T186A);mex-6(RNAi) embryos.…”

“…As the embryo initiates polarization, MBK-2 kinase is activated and phosphorylates a polo-docking site on MEX-5/6, leading to the association of the polo-like kinase PLK-1 with MEX-5/6 (Nishi et al, 2008). This association results in the formation of an anterior-rich PLK-1 gradient that mirrors the MEX-5/6 gradient (Barbieri et al, 2022;Budirahardja et al, 2008;Chase et al, 2000;Nishi et al, 2008;Rivers et al, 2008).…”

Morphogen gradients are regulated by porous media characteristics of the developing tissue

“…Many mathematical models of morphogen gradient formation have been developed over the decades [5, 8, 21, 27, 31, 43, 70, 75, 79, 84, 96, 124, 133]. Current models have, however, not explicitly resolved and studied the 3D porous geometry of the real embryo ECS.…”