Rab7酶和TBC1d5调节Retromer运输的机制研究

Retromer is a conserved coat protein complex (CPC) that controls the retrograde transport of a wide range of endosomal cargoes to TGN or plasma membrane. In contrast to the best-studied CPCs (Clathrin/Adaptor protein, COPI, and COPII) that form cage-like structures, retromer primarily associates with tubular structures. Retromer-dependent transport has been linked with multiple human diseases including neurological disorders, infection, and immunodeficiency; however, molecular mechanisms regulating the function of retromer are very poorly understood. Using integrated approaches including mammalian cell biology, biochemistry, and structural biology, we will characterize the role and functional mechanism of Rab7 and TBC1d5 in retromer-dependent transport. Our study will identify the similarity and difference between retromer and classical CPCs in controlling their assembly and turnover, and help the development of novel diagnosis and treatment of related diseases.

囊泡运输参与细胞多项重要的生命活动,对于生命体的活动必不可少。经典的运输小泡都是球状的，新型的衣被蛋白复合体retromer却形成管状的运输小泡。Retromer调节从内涵体到高尔基网或细胞膜的运输，和人类的许多重大疾病(如神经退行性疾病、感染与免疫缺陷等）的发生发展密切相关。鉴于GTP酶在囊泡运输的关键作用，我们将综合利用细胞生物学，生物化学，结构生物学等手段研究Rab7酶与TBC1d5在Retromer囊泡形成中的功能，结构及分子机制。我们的研究将揭示Retromer与经典囊泡复合物的相同点与不同点，对相关疾病的诊断和治疗作出贡献。