Clathrin-mediated endocytosis (CME) is an essential process in eukaryotes that is important for uptake of nutrients, regulating biochemical signaling pathways, and maintaining the composition and area of the plasma membrane. CME involves the coordination of over 50 different proteins in time and space to produce a deformation of the plasma membrane into a vesicle that is pinched off and internalized. Our lab seeks to understand both the biochemical pathways as well as the physical forces that dictate the initiation, progression and resolution of this process.
Historically, our lab used the budding yeast Saccharomyces cerevisiae as a model system to identify the components and functional modules of the endocytic machinery. Recently, we have been at the forefront of using genome-editing to study CME in an unperturbed state as well as in the development of stem cells as a “model organism” for studying CME in human cells. Current projects include examining how CME changes through differentiation, the study of CME in stem-cell-derived organoids, determining the effect of induced curvature on the dynamics of CME, and using advanced imaging techniques to uncover the ultrastructural organization of the endocytic machinery.
Dambournet, D., Sochacki, K. A., Cheng, A. T., Akamatsu, M., Taraska, J. W., Hockemeyer, D., & Drubin, D. G. (2018). Genome-edited human stem cells expressing fluorescently labeled endocytic markers allow quantitative analysis of clathrin-mediated endocytosis during differentiation. J Cell Biol, jcb-201710084.
Liu, T. L., Upadhyayula, S., Milkie, D. E., Singh, V., Wang, K., Swinburne, I. A., …, Dambournet D., Forster, R., …, Hockemeyer D., Drubin D. G., …, Kirchhausen, T., & Betzig, E. (2018). Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms. Science, 360(6386), eaaq1392.
Zhao, W., Hanson, L., Lou, H.Y., Akamatsu, M., Chowdary, P., Santoro, F., Marks, J., Grassart, A., Drubin, D., Cui, Y. and Cui, B. (2017). Nanoscale manipulation of membrane curvature for probing endocytosis in live cells. Nature Nanotechnology, 12, 750–756.
Hong, S. H., Cortesio, C. L., & Drubin, D. G. (2015). Machine-learning-based analysis in genome-edited cells reveals the efficiency of clathrin-mediated endocytosis. Cell reports, 12(12), 2121-2130.
Peng, Y., Grassart, A., Lu, R., Wong, C. C., Yates, J., Barnes, G., & Drubin, D. G. (2015). Casein kinase 1 promotes initiation of clathrin-mediated endocytosis. Developmental cell, 32(2), 231-240.
Grassart, A., Cheng, A.T., Hong, S.H., Zhang, F., Zenzer, N., Feng, Y., Briner, D.M., Davis, G.D., Malkov, D. and Drubin, D.G. (2014). Actin and dynamin2 dynamics and interplay during clathrin-mediated endocytosis. J Cell Biol, jcb-201403041.