Ayukawa Tomonori, Akiyama Masakazu, Mummery-Widmer Jennifer L, Stoeger Thomas, Sasaki Junko, Knoblich Juergen A, Senoo Haruki, Sasaki Takehiko, Yamazaki Masakazu
Research Center for Biosignal, Akita University, Akita 010-8543, Japan; Department of Cell Biology and Morphology, Akita University Graduate School of Medicine, Akita 010-8543, Japan; Global COE program, Gunma University and Akita University, Akita 010-8543, Japan.
Research Institute for Electronic Science, Hokkaido University, Hokkaido 060-0812, Japan.
Cell Rep. 2014 Jul 24;8(2):610-21. doi: 10.1016/j.celrep.2014.06.009. Epub 2014 Jul 3.
In Drosophila, planar cell polarity (PCP) molecules such as Dachsous (Ds) may function as global directional cues directing the asymmetrical localization of PCP core proteins such as Frizzled (Fz). However, the relationship between Ds asymmetry and Fz localization in the eye is opposite to that in the wing, thereby causing controversy regarding how these two systems are connected. Here, we show that this relationship is determined by the ratio of two Prickle (Pk) isoforms, Pk and Spiny-legs (Sple). Pk and Sple form different complexes with distinct subcellular localizations. When the amount of Sple is increased in the wing, Sple induces a reversal of PCP using the Ds-Ft system. A mathematical model demonstrates that Sple is the key regulator connecting Ds and the core proteins. Our model explains the previously noted discrepancies in terms of the differing relative amounts of Sple in the eye and wing.
在果蝇中,诸如 Dachsous(Ds)等平面细胞极性(PCP)分子可能作为全局方向线索,指导诸如 Frizzled(Fz)等 PCP 核心蛋白的不对称定位。然而,眼睛中 Ds 不对称与 Fz 定位之间的关系与翅膀中的相反,从而引发了关于这两个系统如何连接的争议。在这里,我们表明这种关系由两种 Prickle(Pk)异构体 Pk 和 Spiny-legs(Sple)的比例决定。Pk 和 Sple 形成具有不同亚细胞定位的不同复合物。当翅膀中 Sple 的量增加时,Sple 使用 Ds-Ft 系统诱导 PCP 的逆转。一个数学模型表明,Sple 是连接 Ds 和核心蛋白的关键调节因子。我们的模型根据眼睛和翅膀中 Sple 相对量的不同解释了先前指出的差异。