Li Xue, Wu Yihui, Shen Chenghao, Belenkaya Tatyana Y, Ray Lorraine, Lin Xinhua
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Biochem Biophys Res Commun. 2015 Aug 7;463(4):483-9. doi: 10.1016/j.bbrc.2015.04.151. Epub 2015 May 20.
The Wnt signaling pathway is crucial for development and disease. The regulation of Wnt protein trafficking is one of the pivotal issues in the Wnt research field. Here we performed a genetic screen in Drosophila melanogaster for genes involved in Wingless/Wnt secretion, and identified the p24 protein family members Baiser, CHOp24, Eclair and a v-SNARE protein Sec22, which are involved in the early secretory pathway of Wingless/Wnt. We provided genetic evidence demonstrating that loss of p24 proteins or Sec22 impedes Wingless (Wg) secretion in Drosophila wing imaginal discs. We found that Baiser cannot replace other p24 proteins (CHOp24 or Eclair) in escorting Wg, and only Baiser and CHOp24 interact with Wg. Moreover, we showed that the v-SNARE protein Sec22 and Wg are packaged together with p24 proteins. Taken together, our data provide important insights into the early secretory pathway of Wg/Wnt.
Wnt信号通路对发育和疾病至关重要。Wnt蛋白运输的调控是Wnt研究领域的关键问题之一。在此,我们在黑腹果蝇中对参与无翅型/无翅蛋白(Wingless/Wnt)分泌的基因进行了遗传筛选,并鉴定出参与无翅型/无翅蛋白早期分泌途径的p24蛋白家族成员Baiser、CHOp24、Eclair以及一种v-SNARE蛋白Sec22。我们提供了遗传学证据,证明p24蛋白或Sec22的缺失会阻碍果蝇翅成虫盘内无翅蛋白(Wg)的分泌。我们发现,在护送Wg过程中,Baiser不能替代其他p24蛋白(CHOp24或Eclair),且只有Baiser和CHOp24与Wg相互作用。此外,我们表明v-SNARE蛋白Sec22和Wg与p24蛋白一起被包装。综上所述,我们的数据为Wg/Wnt的早期分泌途径提供了重要见解。