Belenkaya Tatyana Y, Wu Yihui, Tang Xiaofang, Zhou Bo, Cheng Longqiu, Sharma Yagya V, Yan Dong, Selva Erica M, Lin Xinhua
Division of Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Dev Cell. 2008 Jan;14(1):120-31. doi: 10.1016/j.devcel.2007.12.003. Epub 2007 Dec 20.
Secreted Wnt proteins play essential roles in many biological processes during development and diseases. However, little is known about the mechanism(s) controlling Wnt secretion. Recent studies have identified Wntless (Wls) and the retromer complex as essential components involved in Wnt signaling. While Wls has been shown to be essential for Wnt secretion, the function(s) of the retromer complex in Wnt signaling is unknown. Here, we have examined a role of Vps35, an essential retromer subunit, in Wnt signaling in Drosophila and mammalian cells. We provide compelling evidence that the retromer complex is required for Wnt secretion. Importantly, Vps35 colocalizes in endosomes and interacts with Wls. Wls becomes unstable in the absence of retromer activity. Our findings link Wls and retromer functions in the same conserved Wnt secretion pathway. We propose that retromer influences Wnt secretion by recycling Wntless from endosomes to the trans-Golgi network (TGN).
分泌型Wnt蛋白在发育和疾病过程中的许多生物学过程中发挥着重要作用。然而，关于控制Wnt分泌的机制却知之甚少。最近的研究已确定无翅型MMTV整合位点家族（Wntless，Wls）和逆向转运复合物是参与Wnt信号传导的重要组成部分。虽然已证明Wls对Wnt分泌至关重要，但逆向转运复合物在Wnt信号传导中的功能尚不清楚。在这里，我们研究了Vps35（逆向转运复合物的一个必需亚基）在果蝇和哺乳动物细胞的Wnt信号传导中的作用。我们提供了令人信服的证据，表明逆向转运复合物是Wnt分泌所必需的。重要的是，Vps35在内体中共定位并与Wls相互作用。在缺乏逆向转运复合物活性的情况下，Wls变得不稳定。我们的研究结果将Wls和逆向转运复合物的功能联系在同一个保守的Wnt分泌途径中。我们提出，逆向转运复合物通过将Wntless从内体循环到反式高尔基体网络（TGN）来影响Wnt分泌。
