Abstract

Clathrin-mediated endocytosis is a key process by which cells capture nutrients from their environments and down regulate cell surface signaling receptors. It also provides a portal of entry for various intra-cellular pathogens. During this process, the plasma membrane undergoes a series of shape changes that are resisted by membrane tension. In essentially all eukaryotic organisms, a burst of actin assembly accompanies the formation and constriction of deep plasma membrane invaginations during clathrin-mediated endocytosis. The speaker and his research group have studied in yeast and in human stem cells how forces from actin assembly are harnessed to drive these membrane shape changes. For the studies, they use genome-edited human stem cells, live-cell imaging, super-resolution imaging, molecule counting and cryo-EM tomography. All data are fed into mathematical models to reveal which parameters are most critical and to reveal new principles of force generation. The results show that the actin cytoskeleton organizes itself at endocytic sites spontaneously and that actin assembly generates sufficient force to overcome membrane tension. Surprisingly, energy for membrane invagination appears to be stored in bent actin filaments.

About the speaker

Prof. David G. Drubin received his Bachelor’s degree in Biochemistry from the University of California, Berkeley in 1980 and PhD in Biochemistry from the University of California, San Francisco in 1985. He started his career in Massachusetts Institute of Technology as a Postdoctoral Fellow from 1985 to 1988. He then joined the University of California, Berkeley as an Assistant Professor and was promoted to Associate Professor in 1994. He is currently Professor of Cell and Developmental Biology there.

Prof. Drubin was the recipient of the Ernette Comby Chair in Microbiology in 2016. He currently serves as Chair of Scientific Advisory Board in Mechanobiology Institute of National University of Singapore and is also an Editor-in-Chief of Molecular Biology of the Cell. He was elected the Lifetime Achievement Fellow of the American Society for Cell Biology and was appointed as Senior Fellow in Allen Institute for Cell Science in 2016 respectively. He has also been a Member of the American Academy of Arts and Sciences since 2010.

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