An asymmetric pattern of PAR proteins

Nathan Goehring : Mechanochemical coupling between the cytoskeleton and PAR proteins

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A key event in the establishment of PAR polarity in the embryo is the initial induction of asymmetry in the so-called anterior PAR proteins. These proteins are initially segregated into the anterior in association with a dramatic rearrangement of the actomyosin cortex, a thin, highly contractile cytoskeletal layer just under the membrane.

At the onset of polarity, the cortex, which initially forms a highly contractile network throughout the entire embryo, retracts and flows towards the anterior (Figure 1). This flow appears to transport anterior PAR proteins along with it, suggesting that the biochemical PAR network is somehow coupled to the mechanical cytoskeletal network. On the basics of biophysical measurements of PAR proteins and actomyosin motion, we recently provided evidence that this coupling occurs through a process known as advection (Goehring et al. Science 2011).

Importantly, advection does not require direct biochemical interactions between actin and the PAR proteins. Rather, contraction of the actomyosin network results in anterior-directed flows of cortical cytoplasm. PAR proteins that are embedded within this flowing cortical cytoplasm are transported passively much like objects in a river (Figure 2). What properties of PAR proteins allow them to tap into this transport machinery? Conversely, can PAR proteins modulate cortical flows to drive their own transport? A key focus of the lab will be this interplay between these mechanical (cortex) and biochemical (PAR) systems.

A model for advective polarization of a self-organizing PAR chemical network.
Figure 1

Figure 1: A model for advective polarization of a self-organizing PAR chemical network. This model integrates measured kinetic parameters for anterior and posterior PAR proteins including membrane binding and unbinding rates and diffusion coefficients. Further, PARs can exchange between the membrane and a cytoplasmic pool and can displace one another from the membrane.

Given appropriate parameter choice this reaction-diffusion system is multi-stable, capable of supporting either an unpolarized or polarized state. Which state the system will be in, depends on the initial state and what kinds of perturbations are applied. Our work suggests that advection of PAR proteins by cortical cytoplasmic flow can induce asymmetry in the unpolarized state and thereby triggers the system to switch into the polarized state.