On Endocytosis and Loss

06 November 2017 Comments Off on On Endocytosis and Loss


Our bodies are subtle and powerful. Of the countless things that can go wrong with them, very few actually do. But in such cases, where things go awry despite the inbuilt strong self-correcting measures, people are trying to understand what happens. One way to do so is to study the cells that our bodies are made of.
Cells are small compartments enclosed by a lipid membrane. They contain the gooey, slimy stuff of life: proteins, fats, sugars and water. They are grand feats of engineering, but today we will talk, in very shallow terms, about one aspect – their recycling abilities and what can go wrong with them.
Cells recycle the raw materials they have. One of these recycling steps involves swallowing parts of their own membranes and all the material present on the membrane. Think of this as making soap bubbles; you have a bubble blower soaked in detergent and covered with a film. You blow, and a bubble buds off. Now imagine your film of detergent also has some small molecules embedded on the side facing you. When the bubble is blown, the embedded material ends up inside the bubble.
That is how cells take in some molecules that are present on the outside of their membranes. They blow bubbles (or endosomes) into their insides. Once inside, molecular pumps pump acid into the bubble, making the endosome more acidic. The purpose of increasing acidity is to activate molecular scissors that can cut the contents of the endosome into smaller constituents, which can then be recycled by the cell to build new material. And so, the contents of the endosome are completely destroyed.
This is where the insidious villain of our story, the influenza virus, steps into the light. The influenza virus contains genetic material and some proteins encapsulated in a membrane like our own cell membranes. The virus membrane also has proteins (that fold over themselves) sticking out of it. The living dead virus desires nothing more than a new body, a new life. The ultimate aim of the virus is to impregnate host cells with its genetic material, hijack host machinery and consume host resources to create new virus particles that can then hijack other cells, and so on.
Once the influenza virus gains access to our body through our airways, the folded-over protein sticking out of its membrane is able to bind tightly to a protein sticking out of the surface of our cells. When the cell blows bubbles inward, the virus is able to enter as well. But the viral genetic material is now trapped inside two membranes – its own, and that of the bubble the cell created. The genetic material cannot directly pass through the two membranes to reach the proteins inside our cells, which it needs to do in order to kick-start its nefarious plan. To release its genetic material into the cell, the virus uses the cell’s own features.
Remember the folded-over protein sticking out of the virus membrane? As the acidity of the endosome containing the virus increases, the protein is able to change its shape; the folds unfold like a spring. At the end of the chain is a hook that can bury itself in the endosomal membrane. So, the viral membrane becomes attached to the endosomal membrane through this protein, like a boat tethered to the shore by a rope. Next, the “rope” protein collapses again, such that the viral membrane and the endosomal membrane come into close contact. And when this happens, the two membranes can fuse together. Think of this as a smaller bubble inside a larger bubble, with the two fusing into one another. The contents of the smaller bubble (the viral genetic material) can now be released outside the larger bubble (the endosome) into our cells, where they can wreak havoc.
In this way, a cellular pathway for recycling nutrients is harnessed by the influenza virus to destroy the cell. The cell is doomed by what should have protected it.
Such molecular events have parallels in our lives as well.
Remember the story of the man who saw his death in Israel and asked the prophet Solomon to help him escape to India? When he reached India, he found death waiting. Death was surprised to see him at the other end of the world because it had been instructed to find the man in India. The escape was the trap.
Similarly, Harry Potter tried to take steps to prevent his godfather Sirius’s death. And with every bit of care and effort, he walked down the path of causing Sirius’s death.
These are both morbid and dramatic examples, but you have surely seen this process play out in real life. People try to save their loved ones, their relationships, their jobs, their minds, their dreams, but the steps they take to prevent loss only bring about the loss they feared. The harder we try to flee fate, the more inescapable the hole fate digs for us.
Our bodies have tricks to ensure our survival. They work most of the time. But once in a while things go horribly wrong, as when the influenza virus uses the tricks described above. Similarly, our minds have ways of dealing with situations that threaten us. Fear keeps us alive. But sometimes fear causes our minds to lash out, and we enter a cycle where we cause what we tried to prevent. I never understood this before, but perhaps that is why Remus Lupin tells Harry Potter that he is wise to fear fear itself.
Our lives are double-edged swords. To live carefully is to be doomed. To live carelessly is to be doomed. And yet, living is all we know; we cannot help but live. So, we do what we can. We take a deep breath and go on. Knowing fate might have planted a hole in our path. Knowing we might be sacrificing what we hold most dear for what we hold most dear. Like a virus entering a cell, a single event sets us on an inescapable course. We merge into the future of our loss like a viral membrane fusing with an endosomal membrane.