Mannava Anirudh G, Tolwinski Nicholas S
Yale-NUS College and Department of Biological Sciences, National University of Singapore, Block MD6, Centre for Translational Medicine, Yong Loo Lin School of Medicine, 14 Medical Drive, Level 10 South, 10-02M, Singapore 117599, Singapore.
PLoS One. 2015 Apr 7;10(4):e0121879. doi: 10.1371/journal.pone.0121879. eCollection 2015.
Wnt ligands and their downstream pathway components coordinate many developmental and cellular processes. In adults, they regulate tissue homeostasis through regulation of stem cells. Mechanistically, signal transduction through this pathway is complicated by pathway components having both positive and negative roles in signal propagation. Here we examine the positive role of GSK-3/Zw3 in promoting signal transduction at the plasma membrane. We find that targeting GSK-3 to the plasma membrane activates signaling in Drosophila embryos. This activation requires the presence of the co-receptor Arrow-LRP5/6 and the pathway activating protein Disheveled. Our results provide genetic evidence for evolutionarily conserved, separable roles for GSK-3 at the membrane and in the cytosol, and are consistent with a model where the complex cycles from cytosol to membrane in order to promote signaling at the membrane and to prevent it in the cytosol.
Wnt配体及其下游信号通路成分协调许多发育和细胞过程。在成体中，它们通过调节干细胞来维持组织稳态。从机制上讲，该信号通路的信号转导较为复杂，因为通路成分在信号传播中兼具正向和负向作用。在此，我们研究了糖原合成酶激酶3（GSK-3）/糖原合成酶激酶3（Zw3）在促进质膜信号转导中的正向作用。我们发现，将GSK-3靶向质膜可激活果蝇胚胎中的信号传导。这种激活需要共受体箭蛋白-LRP5/6和信号通路激活蛋白散乱蛋白的存在。我们的结果为GSK-3在膜和胞质溶胶中具有进化保守的、可分离的作用提供了遗传学证据，并且与一个模型相符，即该复合物从胞质溶胶循环至膜，以促进膜上的信号传导并在胞质溶胶中阻止信号传导。
