From Flat to Curved

On the picture a 3D reconstruction of a membrane tube is depicted which connects a vesicle to the membran. It was generated artificially by adding the protein endophilin to membranes. Using computer analysis of the images the molecular structure of the tube can be made visible.
Even cells “eat”, by absorbing nutrients from their surroundings. If cells want to absorb large molecules or even whole cells, these are enclosed in round membrane vesicles and transported into the cell’s interior. This important transport mechanism is called endocytosis and is essential for the survival of the cell. Naoko Mizuno and her team are seeking to elucidate, how these vesicles evolve from the membrane.
Endocytosis is a highly dynamic process in which vesicles are constantly formed and re-integrated into the cell membrane or fuse with other membranes inside the cell where they expel their cargo. Naoko Mizuno’s research group is focusing on the fundamental question of how to form a curved vesicle from a flat cell membrane. Therefore, the membrane must be able to bend flexibly. This does not occur spontaneously – the membrane must be actively stabilized.
All about curving
Understanding how this process works has remained elusive until now. When the spherical vesicles bud off from the membrane, they remain connected with the cell membrane via a kind of membrane tube until their final separation. In a study, Naoko Mizuno has already been able to reproduce this process outside the cell. Key factors here were the molecule α-synuclein, endophilin and amphiphysin. These factors form a molecular “spiral staircase” – a long helical structure which embeds itself in the membrane and thus forms it into a small tube – the entry to the inner cell world.
Unwelcome guests
However, the endocytic pathway is not only an essential means of transportation, it also serves as an entry portal for unwelcome guests. Here viruses like HIV and influenza and other dangerous pathogens find their way into the cell. To infect the host cells, all of these pathogens are dependent on endocytosis, meaning that Mizuno’s research is also of high medical relevance.