神经发育对神经网络的建立和大脑功能的维持至关重要。WDR91是在内吞体定位的新蛋白，特异性敲除WDR91的小鼠出现神经发育障碍，但其潜在原因仍知之甚少。由内吞体介导的运输通路是神经发育的必要环节，Retromer复合体和小GTP酶Rab蛋白参与内吞体蛋白分选及转运过程，因此研究WDR91对Retromer复合体和Rab蛋白的影响有利于从内吞体运输的角度揭示WDR91在神经发育中的功能。前期工作发现，缺失WDR91使内吞体依赖于Retromer复合体的逆向运输过程受阻，并且与Rab7结合存在缺陷的WDR91无法恢复这一运输过程。本项目后续工作将深入探究WDR91、Retromer复合体和Rab7三者的调控关系，并进一步阐明WDR91在神经发育中的作用机理。相关结果有望深化内吞体运输对神经发育的作用的认识，为维护胞内蛋白稳态提供有效的方法，为预防和治疗稳态紊乱引发的神经疾病提供潜在的新思路。

Normal neuronal development is essential for the establishment of neural networks and the maintenance of brain function. WDR91 is a novel protein located on endosomes, and brain-specific WDR91 inactivation impairs neuronal development, however the underlying mechanisms are still limited. Endosomal trafficking plays a crucial role in neuronal development, protein sorting and transport are regulated by the Retromer complex and small GTPase Rab proteins. Therefore, investigating the modulation of WDR91 on Retromer complex and Rab protein is helpful to reveal the function of WDR91 for endosomal trafficking and neuronal development. Previous work in this project show that loss of WDR91 causes defects of Retromer-dependent receptors trafficking. In addition, the above trafficking pathway can be rescued by re-expressing WT WDR91 but not the Rab7 binding-deficient WDR91. In this project, we propose to explore the regulatory relationship among WDR91, Retromer complex and Rab7 in detail, and further elucidate the mechanism of WDR91 in neuronal development. Through mechanistic insights into the role of endosomal trafficking in neuronal development, our work may provide effective ways to maintain cellular protein homeostasis and provide potential ways to prevent and treat neurological diseases caused by homeostatic disorders.