Recycling of sorting components (e.g., receptors, SNAREs, transporters etc.) in the endo-lysosome system is essential for the normal assembly and function of the lysosome. The best characterized recycling cargo is yeast Vps10. Vps10, the first member of the Sortilin receptor family, is a transmembrane protein receptor that sorts carboxypeptidase Y (CPY) into vesicles at the Golgi. After CPY-containing vesicles are transported to the endosome, the endosome matures and fuses with the vacuole, delivering soluble CPY to the vacuole lumen. Unlike CPY, which is released from the Vps10 receptor in the endosome, Vps10 is not delivered to the vacuole. It is recycled from the endosome back to the Golgi by retromer, making Vps10 available for additional rounds of CPY sorting. Retromer is an evolutionarily conserved protein coat complex composed of five proteins: Vps5, Vps17, Vps26, Vps29, and Vps35. It deforms the endosomal membrane to form cargo-containing recycling tubules/vesicles. In humans, loss of retromer function is associated with diseases such as neurodegenerative disease. Certain familial Alzheimer’s and Parkinson’s disease patients have a mutation in VPS35. Our lab is interested in understanding how retromer specifically recognizes and sorts its cargo into the recycling tubules/vesicles.
Key Publications
1. Discovery of retromer; Seaman, M.N., McCaffery, J.M., and Emr, S.D. (1998). A membrane coat complex essential for endosome-to-Golgi retrograde transport in yeast. J. Cell Biol. 142, 665-681.
2. Suzuki, S.W., Emr, S.D. (2018). Membrane protein recycling from the vacuole/lysosome membrane. J. Cell Biol. 217(5):1623-1632.
3. Suzuki, S.W.*, Chuang, Y.S.*, Li, M., Seaman, M.N.J., and Emr, S.D. (2019). A bipartite sorting signal ensures specificity of retromer complex in membrane protein recycling. J. Cell Biol. 218(9), 2876-2886.
4. Suzuki, S.W., Oishi, A., Nikulin, N., Jorgensen, J.R., Baile, M.G., Emr, S.D. (2021). A PX-BAR protein Mvp1/SNX8 and a dynamin-like GTPase Vps1 drive endosomal recycling (preprint) bioRxiv 2021.03.11.434991.
