Protein clustering for cell polarity: Par-3 as a paradigm

Abstract

The scaffold protein Par-3 ( Drosophila Bazooka) is a central organizer of cell polarity across animals. This review focuses on how the clustering of Par-3 contributes to cell polarity. It begins with the Par-3 homo-oligomerization mechanism and its regulation by Par-1 phosphorylation. The role of polarized cytoskeletal networks in distributing Par-3 clusters to one end of the cell is then discussed, as is the subsequent maintenance of polarized Par-3 clusters through hindered mobility and inhibition from the opposite pole. Finally, specific roles of Par-3 clusters are reviewed, including the bundling of microtubules, the cortical docking of centrosomes, the growth and positioning of cadherin-catenin clusters, and the inhibition of the Par-6-aPKC kinase cassette. Examples are drawn from Drosophila, Caenorhabditis elegans, mammalian cell culture, and biochemical studies.

Keywords: Par-3 clusters; Protein clustering; cell polarity.

Figure 1.. The organization and polarization of Par-3 clusters.

The oligomerization domain of a Par-3 monomer mediates the formation of a helical fiber from which the linker regions and PDZ domains of Par-3 would emanate like branches of a tree. The space-filling structural model is a Cn3D view of the model of Zhang et al. (PDB: 3ZEE) . Somehow these fibers are organized into local Par-3 clusters scattered across the cell cortex. In the Caenorhabditis elegans one-cell embryo, a polarized actomyosin flow sweeps the Par-3 puncta to one pole, forming the anterior end of the embryo. In the cellularizing Drosophila embryo, a polarized microtubule array positions the Par-3 puncta to one end of each cell, forming the apicolateral domain. Once the polarity of Par-3 clusters is established, it can be maintained by avid interactions between the clusters and the cell cortex combined with inhibition of Par-3 complex formation at the opposite pole by Par-1 phosphorylation. See main text for further details.