Progress in Understanding the “Molecular Scissors” mechanism in Endocytosis – Direct Visualization of Membrane Separation by Dynamin-amphiphysin Complexes is now Possible –
January 26(Fri), 2018
A collaborative research team including Testuya Takeda, Assistant Professor, Kohji Takei, Professor, of the Graduate School of Medicine, Dentistry and Pharmaceutical Sciences at Okayama University, Toshio Ando, Professor at Bio-AFM Frontier Research Center, College of Science and Engineering, Kanazawa University and Takayuki Uchihashi, Specially Appointed Professor in the Graduate School of Science at Nagoya University, discovered the mechanism of membrane separation needed for membrane vesicularization by dynamin-amphiphysin complexes in endocytosis, which is a process whereby a cell transports extracellular molecules into the cell. The research team used a high-speed AFM, a special type of microscope, to bring about a world-first success in achieving the direct visualization of dynamic structural changes within dynamin-amphiphysin complexes in the process of membrane separation. This accomplishment was published in the international science magazine “eLife” at 9:01 am on Tuesday, January 23, 2018, Japan Standard Time.
In the process of endocytosis, a limited area of a cell membrane forms a pocket inside the cell cytoplasm, and this gets separated to form a vesicle. At this time, dynamin, which is a GTPase, and amphiphysin, a type of protein with a BAR domain, form helical complexes in the area of the separated membrane. Then, structural changes, along with GTP hydrolysis, separate the membrane.
The 3D conformation of dynamin and amphiphysin had already been clarified by earlier research through the analysis of crystal structures using X-rays and analysis with cryo-electron microscopy. However, the dynamic structural changes in dynamin-amphiphysin complexes occurring in the process of membrane separation and the mechanism of amphiphysin adjusting the function of dynamin had been unclear.
This research result is expected to support understanding of the pathogenetic mechanisms of currently incurable nerve and muscle diseases as well as understanding membrane remodeling mechanisms in endocytosis.
Authors: Tetsuya Takeda, Toshiya Kozai, Huiran Yang, Daiki Ishikuro, Kaho Seyama, Yusuke Kumagai, Tadashi Abe, Hiroshi Yamada, Takayuki Uchihashi, Toshio Ando, Kohji Takei
Title: Dynamic clustering of dynamin-amphiphysin helices regulates membrane constriction and fission coupled with GTP hydrolysis
Year of Publication: 2018
Okayama University Silicon Valley Office (OUSVO)
Contact: Mototaka Senda, Ph.D.