Polo-like Kinase Couples Cytoplasmic Protein Gradients in the C. elegans Zygote

Abstract

Intracellular protein gradients underlie essential cellular and developmental processes, but the mechanisms by which they are established are incompletely understood. During the asymmetric division of the C. elegans zygote, the RNA-binding protein MEX-5 forms an anterior-rich cytoplasmic gradient that causes the RNA-binding protein POS-1 to form an opposing, posterior-rich gradient. We demonstrate that the polo-like kinase PLK-1 mediates the repulsive coupling between MEX-5 and POS-1 by increasing the mobility of POS-1 in the anterior. PLK-1 is enriched in the anterior cytoplasm and phosphorylates POS-1, which is both necessary and sufficient to increase POS-1 mobility. Regulation of POS-1 mobility depends on both the interaction between PLK-1 and MEX-5 and between MEX-5 and RNA, suggesting that MEX-5 may recruit PLK-1 to RNA in the anterior. The low concentration of MEX-5/PLK-1 in the posterior cytoplasm provides a permissive environment for the retention of POS-1, which depends on POS-1 RNA binding. Our findings describe a novel reaction/diffusion mechanism in which the asymmetric distribution of cytoplasmic PLK-1 couples two RNA-binding protein gradients, thereby partitioning the cytoplasm.

Spindle assembly checkpoint strength is linked to cell fate in theCaenorhabditis elegansembryo

“…PAR protein–mediated cytoplasmic partitioning is regulated by PAR-1, which drives the anterior enrichment of two closely related proteins MEX-5 and MEX-6 (hereafter, MEX-5/6; Griffin et al , 2011 ). MEX-5/6 promote the posterior enrichment and anterior degradation of certain germline determinants ( Schubert et al , 2000 ; Cuenca et al , 2003 ; DeRenzo et al , 2003 ; Wu et al , 2015 ; Han et al , 2018 ) and anchor and enrich other factors in the anterior ( Nishi et al , 2008 ; Han et al , 2018 ). By limiting the accumulation and activity of MEX-5/6 in the posterior ( Schubert et al , 2000 ; Cuenca et al , 2003 ; Griffin et al , 2011 ) and through other MEX-5/6–independent mechanisms (e.g., Cheeks et al , 2004 ; Gallo et al , 2010 ; Benkemoun et al , 2014 ), PAR-1 promotes germline traits in the posterior P 1 cell.…”

Membraneless organelles: P granules in Caenorhabditis elegans

“…When MEX‐5 interacts with PLK‐1 both proteins are relocalized to the anterior. Anterior PLK‐1 kinase activity then either directly or indirectly increases POS‐1, PIE‐1 and MEG‐3 mobility so these factors become posteriorly enriched . Posterior MEG‐3 aggregates resemble a ribbon‐like lattice that could then act as a scaffold for PGL assembly and granule formation .…”

Mitotic Cell Division in Caenorhabditis elegans

“…These include allometry: elucidating how cellular structures modulate and adapt their composition to ensure accurate cell division in differently sized cells (Hara and Kimura 2009;Ladouceur et al, 2017;Lacroix et al 2018), and how cell division processes are coordinated with cell polarity, cell division axis orientation, and cell fate specification to generate appropriate numbers and architectural arrangements of different cell types during development. Importantly, a number of genes required for cell division, such as the polo-like kinase PLK-1, are emerging as important regulators of cell polarity (Noatynska et al 2010;Dickinson et al 2017) and cell fate (Nishi et al 2008;Han et al 2018). The experimental virtues of C. elegans ensure that this elegant animal model will occupy a prominent place in research that further advances our understanding of fundamental cell division processes and their relationship to animal development.…”