Speaker: Sjaak Neefjes
Subject: How do endosomal vesicles move? A surprising interaction network in and between organelles
Location: TU Delft
Author: Renée van der Winden
Sjaak Neefjes came to talk to us about his research on the dynamics of certain endosomes that are active in the immune response of the body. He first explained very briefly what this immune response looks like to get an overview of what he was discussing. Then he focused on the endosomes themselves, how they are formed, how dynamic they are and how they are transported.
When the body is invaded by pathogens, certain macrophages engulf and digest these pathogens and present the pathogen’s antigens on the outside of their own membrane for other cells to see. These macrophages are appropriately called antigen-presenting cells (APCs). Now let’s dive into these APCs. In the Golgi body of the APCs class II MHC proteins are fabricated. It is these proteins that are involved with the presenting of the foreign antigens. These proteins are engulfed in an endosome, which eventually exits the cell, thus presenting the antigens to other cells. These endosomes can have two forms: multivesicular and multilamellar. For now, only multivesicular endosomes were discussed.
One of the questions Sjaak Neefjes discussed is how dynamic these endosomes are. Can proteins leave the endosome after they have been put into it? To test this, green fluorescent protein (GFP) was attached to the MHC II proteins and could thus be seen in the endosomes. Next, protease was added to the GFP expressing cells, so that the proteins were broken up. This resulted in GFP moving from the endosomes to the nucleus. This indicates that, indeed, particles can leave the endosome once they are inside it.
Another subject of this seminar was the movement of these endosomes. They are made somewhere in the center of the cell and have to be moved to the membrane if they are going to be ejected. It appeared this movement happened only in small bursts and was bidirectional. The endosomes can be moved to the outside of the cell, but also back to the center. It was already known that so-called motor proteins exist that bind to endosomes and can transport them across the cell. The questions Sjaak Neefjes discussed was ‘Why do the motor proteins bind the endosome?’ and ‘Why only for a few steps?’. It turns out this is a rather complex interaction of multiple molecules in the cell, which I will not go into right now. In the end, the take-home message was that cholesterol is a key factor in this process. A certain protein in the cell acts as a cholesterol sensor, resulting in endosomes being transported further into the cell when cholesterol binds and endosomes moving to the periphery of the cell when cholesterol does not bind.
I found this seminar quite difficult to follow, because Sjaak Neefjes named a lot of proteins and substances by name. Usually, these names consist simply of letters and numbers, which make a lot of sense if you have been working with them for a long time, but make a talk sound like gibberish at times if you are not familiar with them. I did appreciate that the seminar started with a general overview of the process we were discussing. This places the research into a context that you can wrap your head around as an audience and provides you with a sense of purpose for this research from the start.