Unveiling “nano-scissors” required for endocytosis of synaptic vesicles


The nerve cells that make up a nervous system connect at junctions known as synapses. When a nerve impulse reaches the end of the cell, membrane-bound packages called synaptic vesicles fuse with the surface membrane and release their contents (neurotransmitters) to relay the signal to the next cell. The fused vesicles must be retrieved to make new vesicles, ready to transmit more signals across the synapse using the process known as endocytosis.

Two proteins named dynamin and amphiphysin cooperate in this process. Dynamin is a protein that acts like a motor; it breaks down a molecule called GTP to release energy. Previous studies have shown that dynamin-amphiphysin complexes join end to end to form long helical structures, but their precise mechanism has remained elusive.

Now, Tetsuya Takeda and colleagues at Okayama University, Kanazawa University, and Nagoya University have looked at how the structure of the helices changes during endocytosis.

Using high-speed atomic force microscopy (HS-AFM) that allows imaging of the molecular dynamics in high resolution both in space (sub nm) and time (sub mS), the team successfully imaged dynamic structural changes of dynamin-amphiphysin complexes during membrane fission.

This revealed that the dynamin-amphiphysin helices rearrange to form clusters when the GTP is broken down. Further analysis showed that the folded membrane becomes constricted at regions that are not coated with the clusters of dynamin-amphiphysin helices. The researchers also discovered that amphiphysin controls the size of the clusters to help make the new vesicles more uniform.

These new findings will not only help scientists to better understand the process of endocytosis, but will also give new insights into a number of human diseases affecting the nervous system and muscles caused by defected dynamin function.

Tetsuya Takeda, Toshiya Kozai, Huiran Yang, Daiki Ishikuro, Kaho Seyama, Yusuke Kumagai, Tadashi Abe, Hiroshi Yamada, Takayuki Uchihashi, Toshio Ando, and Kohji Takei

Title of original paper
Dynamic clustering of dynamin-amphiphysin helices regulates membrane constriction and fission coupled with GTP hydrolysis.

Journal, volume, pages and year
eLife 7, e30246 (2018).

Journal, volume, pages and year
eLife 7, e30246 (2018).

Journal, volume, pages and year
eLife 7, e30246 (2018).

Department website

(Figure1)HS-AFM image of clustering dynamin-amphiphysin helices (arrowheads) upon GTP hydrolysis.

(Figure2)Membrane fission occurs at the protein-uncoated regions flanking dynamin-amphiphysin clusters (arrows marked with FP.1 and FP.2)

Figure3)Clusterase model of membrane constriction and fission mediated by dynamin-amphiphysin complexes.marked with FP.1 and FP.2)