Symmetry breaking and polarization of the C. elegans zygote by the polarity protein PAR-2

Abstract

SUMMARYPolarization of the C. elegans zygote is initiated by ECT-2-dependent cortical flows, which mobilize the anterior PAR proteins (PAR-3, PAR-6 and PKC-3) away from the future posterior end of the embryo marked by the sperm centrosome. Here, we demonstrate the existence of a second, parallel and redundant pathway that can polarize the zygote in the absence of ECT-2-dependent cortical flows. This second pathway depends on the polarity protein PAR-2. We show that PAR-2 localizes to the cortex nearest the sperm centrosome even in the absence of cortical flows. Once on the cortex, PAR-2 antagonizes PAR-3-dependent recruitment of myosin, creating myosin flows that transport the anterior PAR complex away from PAR-2 in a positive-feedback loop. We propose that polarity in the C. elegans zygote is initiated by redundant ECT-2-and PAR-2-dependent mechanisms that lower PAR-3 levels locally, triggering a positive-feedback loop that polarizes the entire cortex.

Elaborating polarity: PAR proteins and the cytoskeleton

“…When activity of the ECT-2 RhoGEF is reduced, anterior myosin flows do not occur when polarization would normally begin (Jenkins et al, 2006;Motegi and Sugimoto, 2006;Schonegg and Hyman, 2006). However, Zonies and colleagues noted that ect-2 mutant embryos develop a late, anteriorly directed myosin flow that is accompanied by anterior and posterior PAR domain formation (Zonies et al, 2010). Polarization in ect-2 mutants depends on PAR-2, which loads onto the posterior cortex before the late myosin flow begins.…”

The F-box protein Slmb restricts the activity of aPKC to polarize epithelial cells

“…In this context, Par-2 is the primary antagonist that restricts aPKC/Par activity, while Lgl homologs function in a parallel, redundant role. Par-2 contains a RING finger domain that is characteristic of single-subunit E3 ligases, but Par-2 homologs have not been identified outside of nematodes, Par-2 does not affect aPKC/ Par levels, and a degraded substrate in polarity regulation has yet to be identified (St Johnston and Ahringer, 2010;Zonies et al, 2010). The discovery of a Drosophila E3 ligase with a similar function to Par-2 raises the possibility of a conserved molecular logic to polarity in these two paradigmatic systems; determination of the relevant substrate will shed further light on this question.…”

“…In contrast to the pre-eminent role of the Par complex, multiple protein modules that limit Par activity have been identified in different contexts (Tepass, 2012). In the C. elegans zygote, the protein kinases PAR-1 and PAR-4 act downstream of the RING finger protein PAR-2 to antagonize Par localization and define the posterior cortex (St Johnston and Ahringer, 2010;Zonies et al, 2010). Par-1 and Par-4 (Lkb1 -FlyBase) are also key regulators of fly oocyte polarization, but often have less central roles in other polarized cell types (Haack et al, 2013;Partanen et al, 2013).…”

Cell polarity: models and mechanisms from yeast, worms and flies

“…The position of the sperm centrosome provides a cue that orients the cell by defining the posterior pole in the one-cell zygote. How the sperm centrosome acts as a polarity cue (see Glossary, Box 1) is still not fully understood, as there appear to be multiple redundant mechanisms at work (Cowan and Hyman, 2007;Zonies et al, 2010;Motegi et al, 2011). Nevertheless, the key polarity determinants that respond to these early signals and maintain polarity were discovered in pioneering genetic screens for mutants that affect the asymmetric partitioning of granules during the first cell division (Kemphues et al, 1988).…”