Chowdury, Debanjan, Nicola, Ernesto, Grill, Stephan W., Khuc-Trong, Philip, Hyman, Anthony A, Goehring, Nathan W.
[
International Worm Meeting,
2009]
A conserved network of PAR polarity proteins is required for establishment of cellular polarity in a wide variety of systems. These proteins are typically segregated into mutually exclusive, functionally distinct membrane domains which define the axis of polarity. In the one-celled C. elegans embryo, discrete sets of PAR proteins are partitioned into roughly equal sized anterior and posterior domains, which are essential for the proper inheritance of cell fate determinants during the asymmetric first cell division. The formation of PAR domains has been shown to depend on a highly contractile cortical actomyosin network that is itself polarized and is required for establishing PAR polarity. PAR domains also depend on mutual antagonistic interactions between PAR proteins, which are essential for maintaining their stable, mutually exclusive distribution within discrete domains. However, despite progress in understanding the molecular activities involved in these processes, we lack a basic physical mechanism for explaining how the activities of the actomyosin cortex and the PAR proteins are coupled in order to give rise to the stable, reproducibly sized PAR domains that are observed in the embryo. In order to provide insight into the types of mechanisms that could underlie the formation of PAR domains, we undertook a quantitative description of the dynamics of PAR proteins in C. elegans embryos. The results of this analysis indicate that PAR proteins diffuse extensively on the membrane of embryos, exchange between membrane-associated and cytoplasmic states, and are subject to advection by actomyosin-dependent cortical flow. We find that these observed behaviors, when coupled to the documented antagonism between PAR proteins, are sufficient to generate a reaction-diffusion driven system for establishing PAR polarity. The theoretical model we propose provides a single, rather simple physical mechanism that explains the actomyosin-dependent polarization of the embryo, the maintenance of mutually exclusive PAR domains, and the reproducible determination of domain size. Importantly, in this model the stable partitioning of the embryo into domains is a function of intrinsic properties of the PAR proteins and does not appear to depend on an underlying scaffold function of the actomyosin cortex. Rather, this work suggests that the actomyosin cortex acts primarily through the generation of cortical flow which provides a robust trigger to ensure that polarization of the PAR system occurs with the proper timing and geometry.