Rapid Disruption of Dishevelled Activity Uncovers an Intercellular Role in Maintenance of Prickle in Core Planar Polarity Protein Complexes

Abstract

Summary: Planar polarity, the coordinated polarization of cells in the plane of a tissue, is important for normal tissue development and function. Proteins of the core planar polarity pathway become asymmetrically localized at the junctions between cells to form intercellular complexes that coordinate planar polarity between cell neighbors. Here, we combine tools to rapidly disrupt the activity of the core planar polarity protein Dishevelled, with quantitative measurements of protein dynamics and levels, and mosaic analysis, to investigate Dishevelled function in maintenance of planar polarity. We provide mechanistic insight into the hierarchical relationship of Dishevelled with other members of the core planar polarity complex. Notably, we show that removal of Dishevelled in one cell causes rapid release of Prickle into the cytoplasm in the neighboring cell. This release of Prickle generates a self-propagating wave of planar polarity complex destabilization across the tissue. Thus, Dishevelled actively maintains complex integrity across intercellular junctions. : Ressurreição et al. have developed tools to rapidly disrupt protein function in Drosophila and used these to investigate the function of the protein Dishevelled in planar polarity. They find a continuous requirement for Dishevelled in core planar polarity complex maintenance with its loss causing relocalization of Prickle in neighboring cells. Keywords: planar polarity, planar cell polarity (PCP), signaling, disheveled, prickle, Drosophila, genetic tools