Rapid diffusion-state switching underlies stable cytoplasmic gradients in the Caenorhabditis elegans zygote

Rapid diffusion-state switching underlies stable cytoplasmic gradients in the Caenorhabditis elegans zygote

Protein concentration gradients organize cells and tissues and commonly form through diffusion away from a local source of protein. Interestingly, during the asymmetric division of the Caenorhabditis elegans zygote, the RNA-binding proteins MEX-5 and PIE-1 form opposing concentration gradients in the absence of a local source.

Our findings suggest that both proteins interconvert between fast-diffusing and slow-diffusing states on timescales that are much shorter (seconds) than the timescale of gradient formation (minutes). The kinetics of diffusion-state switching are strongly polarized along the anterior/posterior (A/P) axis by the PAR polarity system such that fast-diffusing MEX-5 and PIE-1 particles are approximately symmetrically distributed, whereas slow-diffusing particles are highly enriched in the anterior and posterior cytoplasm, respectively. Using mathematical modeling, we show that local differences in the kinetics of diffusion-state switching can rapidly generate stable concentration gradients over a broad range of spatial and temporal scales.

Intracellular concentration gradients regulate essential processes including the organization of the mitotic spindle, cytokinesis, and cell polarity. Unlike tissue-scale gradients, little is known about how intracellular gradients form.

rapid diffusion-state switching can quickly pattern gradients across a range of temporal and spatial scales.

Some intracellular gradient-forming mechanisms appear to rely on reactions that occur at the cell boundary/cell pole.

In principle, gradient formation through rapid diffusion-state switching could provide a general means by which gradients are rapidly patterned across a wide range of temporal and spatial scales.

it will be interesting to learn to what extent other gradients are a cause or a consequence of a protein’s spatially graded binding activity.

How are the “local differences in the kinetics of diffusion-state switching” produced?