内体溶酶体主要是由次级内体和溶酶体融合形成的细胞器，在内吞途径中发挥重要作用。内体溶酶体的异常增大将会阻碍正常的囊泡运输和导致神经退行性疾病。然而，内体溶酶体形态调控机制的研究依然处在起步阶段。最近的研究发现，SNX10的过表达可以促进内体溶酶体的异常增大，而SNX11可以抑制SNX10引起的内体溶酶体增大。本实验室最近报道了SNX10和SNX11的晶体结构，但是SNX10和SNX11调节内体溶酶体形态的分子机制仍不清楚。本课题将用双分子荧光互补技术等细胞生物学手段筛选SNX10和SNX11的相互作用蛋白，从而完善内体溶酶体形态调控网络；进一步解析SNX10/SNX11与相互作用蛋白复合物晶体结构，从而阐明SNX10/SNX11调节内体溶酶体形态的分子机制。目前，我们完成了SNX11相互作用蛋白的筛选和高通量测序，正在进行体外验证。这些前期工作，为我们顺利完成本项目奠定了基础。

Endo-lysosomes, formed by fusion of endosome with lysosome, play critical roles in the degradation of internalized cargo. The enlarged endo-lysosomes are proposed to interfere with normal vesicle trafficking and lead to neuro-degeneration. Therefore, endo-lysosome biogenesis and morphology regulation are critical to human health. Up to date, the mechanism of endo-lysosome morphology regulation is still unclear. It has been reported that over-expressed SNX10 can induce endo-lysosome enlargement, while SNX11 can inhibit SNX10-induced endo-lysosome enlargement. We recently reported the crystal structures of SNX10 and SNX11. However, the mechanism of SNX10 and SNX11 regulating endo-lysosome morphology is still unknown. In this project, we aim to identify partner proteins for SNX10 and SNX11 using bimolecular fluorescence complementation (BiFC) and elucidate the mechanism of SNX10 and SNX11 regulating endo-lysosome morphology. Currently, we finished screening and sequencing of SNX11 partner proteins.