Dept. of Cell, Developmental, & Regenerative Biology,Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Dept. of Molecular Biology Princeton University, Princeton, New Jersey, United States of America.
PLoS Genet. 2023 Jul 18;19(7):e1010849. doi: 10.1371/journal.pgen.1010849. eCollection 2023 Jul.
Epithelial tissues can be polarized along two axes: in addition to apical-basal polarity they are often also polarized within the plane of the epithelium, known as planar cell polarity (PCP). PCP depends upon the conserved Wnt/Frizzled (Fz) signaling factors, including Fz itself and Van Gogh (Vang/Vangl in mammals). Here, taking advantage of the complementary features of Drosophila wing and mouse skin PCP establishment, we dissect how Vang/Vangl phosphorylation on a specific conserved tyrosine residue affects its interaction with two cytoplasmic core PCP factors, Dishevelled (Dsh/Dvl1-3 in mammals) and Prickle (Pk/Pk1-3). We demonstrate that Pk and Dsh/Dvl bind to Vang/Vangl in an overlapping region centered around this tyrosine. Strikingly, Vang/Vangl phosphorylation promotes its binding to Prickle, a key effector of the Vang/Vangl complex, and inhibits its interaction with Dishevelled. Thus phosphorylation of this tyrosine appears to promote the formation of the mature Vang/Vangl-Pk complex during PCP establishment and conversely it inhibits the Vang interaction with the antagonistic effector Dishevelled. Intriguingly, the phosphorylation state of this tyrosine might thus serve as a switch between transient interactions with Dishevelled and stable formation of Vang-Pk complexes during PCP establishment.
除了顶端-基底极性之外，它们通常在上皮平面内也具有极性，称为平面细胞极性（PCP）。PCP 依赖于保守的 Wnt/Frizzled（Fz）信号因子，包括 Fz 本身和梵高（Vang/Vangl 在哺乳动物中）。在这里，利用果蝇翅膀和小鼠皮肤 PCP 建立的互补特征，我们剖析了 Vang/Vangl 在特定保守酪氨酸残基上的磷酸化如何影响其与两个细胞质核心 PCP 因子，Dishevelled（Dsh/Dvl1-3 在哺乳动物中）和 Prickle（Pk/Pk1-3）的相互作用。我们证明 Pk 和 Dsh/Dvl 在以该酪氨酸为中心的重叠区域与 Vang/Vangl 结合。引人注目的是，Vang/Vangl 磷酸化促进其与 Prickle 的结合，Prickle 是 Vang/Vangl 复合物的关键效应物，并抑制其与 Dishevelled 的相互作用。因此，该酪氨酸的磷酸化似乎在上皮细胞极性建立过程中促进成熟的 Vang/Vangl-Pk 复合物的形成，相反，它抑制了 Vang 与拮抗效应物 Dishevelled 的相互作用。有趣的是，该酪氨酸的磷酸化状态可能是在上皮细胞极性建立过程中，与 Dishevelled 的瞬时相互作用和 Vang-Pk 复合物的稳定形成之间的一种开关。
