Intracellular Nanovesicles: their formation, transport and cargo

Lead Research Organisation: University of Warwick
Department Name: Warwick Medical School

Abstract

Humans are built from lots of cells. Rather than being boring building blocks, the interior of each cell is a busy world where proteins are made and go to work, constantly moving around. This allows each cell to eat, drink, reproduce, and much more. We are interested in the cell's membrane trafficking system: a transport network of different types of membrane vesicles that important proteins can travel in. Membrane trafficking ensures that cargo proteins go to the right place at the right time. This keeps cells functioning healthily and normally. We recently found a new type of vesicle and we now want to understand it in more detail. These vesicles are called intracellular nanovesicles, or INVs for short. In cells, when a vesicle is formed, it gathers the proteins that it will take and buds from its origin. It must then be transported to its destination where it fuses with the target membrane. You can think of this as the vesicle's life cycle: they are born, they travel and then they die when they deliver their important cargo. In this project we want to document the life story of INVs. We will focus on their "early years". How are they born? How do they travel? Which friends do they carry along the way? Very little is known about INVs because they were only recently discovered. The details of the life story of INVs is likely to change how cell biologists think about the membrane traffic system.

Technical Summary

Membrane trafficking is crucial to eukaryotic life. The membrane traffic system is a network of vesicles that ensures proteins are moved to the right place at the right time. This process controls many important cellular functions, for example, cell signalling or motility. We have recently found a new class of transport vesicle, termed intracellular nanovesicles (INVs). These small vesicles are widespread in the membrane trafficking system and play a role in anterograde traffic, Golgi integrity and recycling of endocytosed material. Due to their recent discovery, there is a lot to learn about these vesicles. For example, how do they form? How are they transported? What cargos do they carry? We will answer these questions in this project using a combination of state-of-the-art imaging methods (super-resolution microscopy and electron microscopy), genetically encoded probes and proteomics. Understanding INVs in more detail is therefore likely to have wide impact in the membrane trafficking field and on cell biology in general.

Planned Impact

The Pathways to Impact document sets out our five directions to maximise the impact of our discoveries. These are: 1) public presentations - publications, talks, and seminars; 2) interactions with the general public - lab tours and outreach events; 3) online promotion - web-based promotion of results; 4) press releases - engaging the press office to publicise our discoveries; and 5) sharing resources - plasmids and code.
We have three specific objectives. 1) To generate 3D models relevant to our work for a hands-on outreach experience. 2) Make a video abstract for each of the papers from this project, to publicise our work online. 3) To discuss dissemination of our work with the press team. A timeline is included to describe our impact plan throughout the project.

Publications

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