Research Group "Cellular and Membrane Trafficking" (Naoko Mizuno)
Even cells “eat”, by absorbing nutrients from their surroundings. Smaller molecules diffuse directly through the cell membrane or can be transported via membrane channels. However, large chunks are difficult to swallow. 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. Naoko Mizuno and her Research Group “Cellular and Membrane Trafficking” are seeking to elucidate this key transport mechanism (endocytosis) in detail. Endocytosis is one of the most important means of cellular transport and is a highly dynamic process. The vesicles therefore are seldom long-lasting: They are re-integrated into the cell membrane or fuse with other membranes inside the cell where they expel their cargo. Endocytosis also aids in sorting and recycling cellular proteins, whereby vesicles are constantly formed and dissolved again. Naoko Mizuno’s Research Group is focusing on the fundamental question of how membranes can form curved structures out of which vesicles later arise.
Cell membranes are not rigid envelopes but rather consist of “floating” lipid layers, which are often interspersed with proteins. In order to form a curved vesicle from a flat cell membrane, the membrane must be able to bend flexibly. This does not occur spontaneously – the membrane must be actively stabilized. Understanding how this process works has remained elusive until now. Naoko Mizuno is seeking to shed light on this process by elucidating the mechanisms of endocytosis. In her investigations she uses different methods of biophysics and structural biology, which she combines and develops further for specific applications. Core techniques are X-ray crystallography and imaging techniques such as light microscopy and cryo-electron microscopy. Scientists can visualize large molecular complexes such as vesicles in their original structure and surroundings using cryo-electron microscopy – and this in high resolution.
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 molecules α-synuclein, endophilin and amphiphysin, which stabilize the curved membrane surface so that a cylindrical structure can arise. 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.
However, the endocytic pathway is not only an essential means of transportation to absorb larger-sized nutrient particles, 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.