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PAR-2, LGL-1 and the CDC-42 GAP CHIN-1 act in distinct pathways to maintain polarity in the C. elegans embryo.

ABSTRACT: In the one-cell C. elegans embryo, polarity is maintained by mutual antagonism between the anterior cortical proteins PAR-3, PKC-3, PAR-6 and CDC-42, and the posterior cortical proteins PAR-2 and LGL-1 on the posterior cortex. The mechanisms by which these proteins interact to maintain polarity are incompletely understood. In this study, we investigate the interplay among PAR-2, LGL-1, myosin, the anterior PAR proteins and CDC-42. We find that PAR-2 and LGL-1 affect cortical myosin accumulation by different mechanisms. LGL-1 does not directly antagonize the accumulation of cortical myosin and instead plays a role in regulating PAR-6 levels. By contrast, PAR-2 likely has separate roles in regulating cortical myosin accumulation and preventing the expansion of the anterior cortical domain. We also provide evidence that asymmetry of active CDC-42 can be maintained independently of LGL-1 and PAR-2 by a redundant pathway that includes the CDC-42 GAP CHIN-1. Finally, we show that, in addition to its primary role in regulating the size of the anterior cortical domain via its binding to PAR-6, CDC-42 has a secondary role in regulating cortical myosin that is not dependent on PAR-6.

SUBMITTER: Beatty A

PROVIDER: S-EPMC3631973 | biostudies-literature |

REPOSITORIES: biostudies-literature

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CGEF-1 and CHIN-1 regulate CDC-42 activity during asymmetric division in the Caenorhabditis elegans embryo.

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Project description:At the one-cell stage, the C. elegans embryo becomes polarized along the anterior-posterior axis. The PAR proteins form complementary anterior and posterior domains in a dynamic process driven by cytoskeletal rearrangement. Initially, the PAR proteins are uniformly distributed throughout the embryo. After a cue from fertilization, cortical actomyosin contracts toward the anterior pole. PAR-3/PAR-6/PKC-3 (the anterior PAR proteins) become restricted to the anterior cortex. PAR-1 and PAR-2 (the posterior PAR proteins) become enriched in the posterior cortical region. We present a mathematical model of this polarity establishment process, in which we take a novel approach to combine reaction-diffusion dynamics of the PAR proteins coupled to a simple model of actomyosin contraction. We show that known interactions between the PAR proteins are sufficient to explain many aspects of the observed cortical PAR dynamics in both wild-type and mutant embryos. However, cytoplasmic PAR protein polarity, which is vital for generating daughter cells with distinct molecular components, cannot be properly explained within such a framework. We therefore consider additional mechanisms that can reproduce the proper cytoplasmic polarity. In particular we predict that cytoskeletal asymmetry in the cytoplasm, in addition to the cortical actomyosin asymmetry, is a critical determinant of PAR protein localization.

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