The biochemical and cellular dynamics of polarity proteins during asymmetric cell division

The Par complex regulates the polarity of diverse animal cells, such as in the Drosophila neuroblast where it polarizes fate determinants during asymmetric divisions. Par localization is dynamic since it has been known to exist in the neuroblast cytoplasm during interphase before becoming highly polarized to the neuroblast's apical cortex by metaphase. Very little has been known about how the complex repeatedly transitions between unpolarized and polarized states. I will present data demonstrating that the establishment and breakdown of Par polarity are both complex, multistep processes involving distinct highly dynamic intermediates with transitions that likely involve actomyosin. Polarization of the Par complex in neuroblasts and other cells requires the Par-3 protein, which is a substrate of the Par complex member atypical Protein Kinase C (aPKC). Recently, Par-3 has been proposed to act as an “inhibitory substrate” of this kinase, in which its short substrate peptide occupies the kinase’s active site without being phosphorylated. I will present data showing that Par-3 is readily phosphorylated by aPKC and discuss the implications of this biochemical event on the possible mechanisms by which Par-3 polarizes the Par complex.