MRC Centre for Developmental and Biomedical Genetics and Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield, United Kingdom.
PLoS Genet. 2013;9(7):e1003654. doi: 10.1371/journal.pgen.1003654. Epub 2013 Jul 18.
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.
核心平面极性蛋白需要指定在上皮平面极化的结构的方向。在黑腹果蝇的翅膀中，核心蛋白在近端或远端细胞边缘不对称地定位。不对称的定位被认为是由长程线索偏向的，导致不对称的复合物与组织轴对齐。然后，核心蛋白被认为参与了放大不对称性所必需的反馈相互作用，为了使这种反馈相互作用能够正确运行，在连接点处的核心蛋白的水平必须受到严格的调节。我们已经研究了蛹翅中核心蛋白 Prickle（Pk）的调节。核心蛋白斜视（Stbm）需要将 Pk 招募到近端细胞末端的不对称复合物中，我们在这里报告它还促进了多余 Pk 的蛋白酶体降解，可能是通过 Cullin-1 依赖的过程。我们还首次表明 Pk 在体内被法呢基化，这对于 Pk 在翅膀中的功能是必不可少的。值得注意的是，Pk 的法呢基化对于它被招募到不对称复合物中并在反馈放大中发挥作用是必要的，这可能是通过加强 Stbm 和 Pk 之间的弱直接相互作用来实现的。此外，法呢基化对于 Stbm 促进 Pk 的蛋白酶体降解也是必需的。我们提出 Stbm 将法尼基化的 Pk 招募到不对称复合物中，但也促进了多余 Pk 的降解，否则会破坏反馈放大。
