PAR-1 is a highly conserved serine/threonine kinase involved in the polarisation of many cell types. Although PAR-1 is central to the polarisation process, the mechanisms that spatially regulate PAR-1 activity are still poorly understood. Now, Andrew Folkmann and Geraldine Seydoux examine PAR-1 regulation in the C. elegans zygote, which is polarised to undergo asymmetric, asynchronous cell divisions. Using CRISPR genome editing, the authors GFP-tag the par-1 locus and generate mutant proteins to visualise PAR-1 localisation. PKC-3-mediated phosphorylation of PAR-1 forms a posterior-rich gradient in the zygote. Indeed, PAR-1::GFP(T983A), which cannot be phosphorylated, is distributed uniformly throughout the zygote, and results in symmetric and synchronous divisions. However, the zygotes do retain some polarity, including transient asymmetrical distribution of PAR-1 targets, such as MEX-5. This residual asymmetric activity requires an autoinhibitory domain in PAR-1 (KA1) that suppresses PAR-1's kinase activity. When regulation of PAR-1 by PKC-3 is functional, the KA1 domain is not essential for polarisation of the zygote, but is required for blastomere polarisation after the 4-cell stage and for fertility. Together, these data suggest that robust asymmetric PAR-1 activity requires regulation of both the localisation and activity of PAR-1 by PKC-3 and the KA1 domain, respectively.
Parallel processes for PAR-1-dependent polarity
Parallel processes for PAR-1-dependent polarity. Development 15 March 2019; 146 (6): e0603. doi:
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