Strabismus Promotes Recruitment and Degradation of Farnesylated Prickle in Drosophila melanogaster Planar Polarity Specification

摘要

The core planar polarity proteins are required to specify the orientation of structures that are polarised in the plane of the epithelium. In the Drosophila melanogaster wing, the core proteins localise asymmetrically at either proximal or distal cell edges. Asymmetric localisation is thought to be biased by long-range cues, causing asymmetric complexes to become aligned with the tissue axes. Core proteins are then thought to participate in feedback interactions that are necessary to amplify asymmetry, and in order for such feedback interactions to operate correctly, the levels of the core proteins at junctions must be tightly regulated. We have investigated regulation of the core protein Prickle (Pk) in the pupal wing. The core protein Strabismus (Stbm) is required to recruit Pk into asymmetric complexes at proximal cell ends, and we report here that it also promotes proteasomal degradation of excess Pk, probably via a Cullin-1 dependent process. We also show for the first time that Pk is farnesylated in vivo , and this is essential for Pk function in the wing. Notably, farnesylation of Pk is necessary for it to be recruited into asymmetric complexes and function in feedback amplification, probably by reinforcing weak direct interactions between Stbm and Pk. Furthermore, farnesylation is also required for Stbm to promote proteasomal degradation of Pk. We propose that Stbm recruits farnesylated Pk into asymmetric complexes, but also promotes degradation of excess Pk that would otherwise perturb feedback amplification. Author Summary The core planar polarity proteins are responsible for polarising structures in the plane of epithelia. For example in the fly wing, the core proteins are required for cells to make hairs that point towards the distal end of the wing. The core proteins localise asymmetrically in wing cells, either at the distal cell end where the hair emerges or at the opposite cell edge. To establish this asymmetric localisation the core proteins must undergo feedback interactions with each other, and it is thought that for feedback to operate correctly, the amounts of the core proteins at junctions must be limiting. We show that the core protein Prickle is modified by a farnesyl lipid molecule. This modification is essential for it to associate with cell membranes where it can interact with another core protein, Strabismus. Interaction with Strabismus allows Prickle to participate in asymmetric complexes and feedback interactions, but Strabismus also causes degradation of excess Prickle. If Prickle doesn't interact with Strabismus, or if there is too much Prickle at cell membranes, asymmetric localisation of the other core proteins is compromised.