Anterior PAR proteins function during cytokinesis and maintain DYN‐1 at the cleavage furrow in Caenorhabditis elegans

Abstract

PAR proteins are key regulators of cellular polarity and have links to the endocytic machinery and the actin cytoskeleton. Our data suggest a unique role for PAR proteins in cytokinesis. We have found that at the onset of cytokinesis, anterior PAR-6 and posterior PAR-2 proteins are redistributed to the furrow membrane in a temporal and spatial manner. PAR-6 and PAR-2 localize to the furrow membrane during ingression but PAR-2-GFP is distinct in that it is excluded from the extreme tip of the furrow. Once the midbody has formed, PAR-2-GFP becomes restricted to the midbody region (the midbody plus the membrane flanking it). Depletion of both anterior PAR proteins, PAR-3 and PAR-6, led to an increase in multinucleate embryos, suggesting that the anterior PAR proteins are necessary during cytokinesis and that PAR-3 and PAR-6 function in cytokinesis may be partially redundant. Lastly, anterior PAR proteins play a role in the maintenance of DYN-1 in the cleavage furrow. Our data indicate that the PAR proteins are involved in the events that occur during cytokinesis and may play a role in promoting the membrane trafficking and remodeling events that occur during this time.

The PAR network: redundancy and robustness in a symmetry-breaking system

“…As in symmetry breaking, the PAR boundary follows actomyosin flows into the cytokinetic furrow. Recent observations indicate that PAR-3 and PAR-6 are required partially redundantly for successful cytokinesis and may play a role in spatial organization of the cytokinetic furrow [82]. …”

Cortical PAR polarity proteins promote robust cytokinesis during asymmetric cell division

“…In C. elegans , depletion of PAR-2 enhances contractile ring constriction defects caused by compromised spindle signaling ( Dechant and Glotzer, 2003 ; Verbrugghe and White, 2007 ). Moreover, both the aPAR and pPAR proteins “track” with the contractile ring during cytokinesis ( Schenk et al, 2010 ; Pittman and Skop, 2012 ).…”

Going with the flow: insights fromCaenorhabditis eleganszygote polarization

“…Here we have described self-organising systems that rely on biochemical networks and mechanochemical feedback loops. These drive pulsatility of the actomyosin cortex, key to the patterning of the C. elegans zygote as well as to morphogenetic processes such as those involved in the Drosophila embryo and in mammalian blastocyst compaction [70,94,95,154,155,159,[165][166][167]169] Similar mechanochemical feedbacks may also operate between actomyosin flows and patterning domains in asymmetrically dividing cells to ensure correct segregation and inheritance of polarity effectors and cell fate determinants [65,82,96,117,119,146,199,200,261,263,272,275,278,279] Spatiotemporal regulation of protein clustering at the membrane is an emerging mechanism that can regulate sensitivity of proteins to patterning flows. Clustering of PAR proteins may reduce their diffusion in the plane of the membrane and their dissociation rates from the membrane, granting PARs the ability to tap into cortical flows [54][55][56][57] (Sailer 2015, Dickinson, Schwager 2017, Rodriguez, Peglion 2017, Wang, Low 2017).…”

“…These drive pulsatility of the actomyosin cortex, key to the patterning of the C. elegans zygote as well as to morphogenetic processes such as those involved in the Drosophila embryo and in mammalian blastocyst compaction [70,94,95,154,155,159,[165][166][167]169]. Similar mechanochemical feedbacks may also operate between actomyosin flows and patterning domains in asymmetrically dividing cells to ensure correct segregation and inheritance of polarity effectors and cell fate determinants [65,82,96,117,119,146,199,200,262,264,273,276,279,280].…”

“…Processes leading to cell division can also reposition the PAR domain boundary to ensure correct segregation and inheritance of these patterning proteins. In the C. elegans zygote, errors in the relative sizes of aPAR and pPAR cortical domains and thus the position of the boundary between them can be corrected during anaphase to match the cleavage furrow [96,279,280]. This polarity domain correction is regulated by Gα, which facilitates cortical flows via astral MT-cortex interactions [255,[280][281][282].…”