Undelivered items go to BAG6

A story of how bin men work at the post office in our cells

Our cells produce all sorts of proteins with all sorts of functions. But to fulfil these functions the proteins must be in the right place. There’s no use for a protein that should be in the nucleus to stick around the outer membrane and like wise. When a protein needs to go to a specific compartment of the cell, this information is encoded in the protein itself. It’s like the address on an envelope. And interestingly, the machinery responsible for protein delivery starts working even before the synthesis of the protein is finished. It’s like we addressed an envelope, then started writing a letter, and before we finished it, our personal postman was already putting the address from the envelope into his sat nav.
Because there is so many various proteins being synthesised in the cell at any given moment, these postmen sometimes can’t keep up and happen miss a “protein letter”. The protein would then just stick around and clutter the wrong compartment of the cell. Now obviously, apart from post men, our cells are also equipped with bin men, who take care of such undelivered protein mail. A recent discovery (1) found that these bin men are actually very vigilant and work in a fashion very similar to the postmen. They hang around the protein factories, and as soon as they see a protein addressed to the membrane that wasn’t spotted by any of the postmen, they grab it and put it in their trash bag. Interestingly, one of the proteins responsible for this process is called BAG6.
You might wonder, is this discovery really that important? Isn’t it science just for the sake of it? Would a cell really mind having some litter laying around its protein synthesis offices? Well, actually, it would. Apart from just not being able to fulfil its function at the right compartment of the cell, a protein that isn’t where it’s supposed to be, can behave in an unpredicted and sometimes harmful way. This is one of the causes for Creutzfeldt-Jakob disease, otherwise known as the human form of mad cow disease. A so-called prion protein, the cause of this disease, is normally supposed to find itself in the cell membrane. But when it doesn’t and stays in the cell cytoplasm (where protein synthesis occurs) it tends to form aggregates which are very resistant to being cleaned up. These aggregates start affecting the functioning of the whole cell, and because the protein is mainly produced in the brain cells, the brain’s function gets severely impaired. If this research goes further, maybe the scientists will be able to better understand the onset of the disease, and maybe even come up with novel therapies to either treat patients affected by it, or prevent its development in people who have a family history.
So that’s the story. In our cells, bin men work as fast as they can to remove junk proteins which are undelivered. And wouldn’t it be great if all the junk mail we receive was binned just as it’s being put in its envelope?

1. Protein targeting and degradation are coupled for elimination of mislocalized proteins.