Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers-The State University of New Jersey, Piscataway, NJ 08854, USA.
Curr Biol. 2012 Jul 24;22(14):1302-8. doi: 10.1016/j.cub.2012.05.049. Epub 2012 Jun 21.
The Fat pathway controls both planar cell polarity (PCP) and organ growth. Fat signaling is regulated by the graded expression of the Fat ligand Dachsous (Ds) and the cadherin-domain kinase Four-jointed (Fj). The vectors of these gradients influence PCP, whereas their slope can influence growth. The Fj and Ds gradients direct the polarized membrane localization of the myosin Dachs, which is a crucial downstream component of Fat signaling. Here we show that repolarization of Dachs by differential expression of Fj or Ds can propagate through the wing disc, which indicates that Fj and Ds gradients can be measured over long range. Through characterization of tagged genomic constructs, we show that Ds and Fat are themselves partially polarized along the endogenous Fj and Ds gradients, providing a mechanism for propagation of PCP within the Fat pathway. We also identify a biochemical mechanism that might contribute to this polarization by showing that Ds is subject to endoproteolytic cleavage and that the relative levels of Ds isoforms are modulated by Fat.
脂肪通路既控制平面细胞极性（PCP）又控制器官生长。脂肪信号由脂肪配体 Dachsous（Ds）和钙粘蛋白结构域激酶 Four-jointed（Fj）的梯度表达调控。这些梯度的向量影响 PCP，而它们的斜率则可以影响生长。Fj 和 Ds 梯度指导肌球蛋白 Dachs 的极化膜定位，这是脂肪信号的关键下游成分。在这里，我们表明 Fj 或 Ds 的差异表达可以使 Dachs 重新极化，从而在翅膀盘中传播，这表明 Fj 和 Ds 梯度可以在长距离上进行测量。通过对标记基因组构建体的表征，我们表明 Ds 和 Fat 本身沿着内源性 Fj 和 Ds 梯度部分极化，为 Fat 通路内 PCP 的传播提供了一种机制。我们还通过显示 Ds 受到内肽酶切割以及 Ds 同工型的相对水平受 Fat 调节，鉴定了一种可能有助于这种极化的生化机制。
