Brain cells share information with virus-like capsules

Friday, February 2nd, 2018

We still don’t know how the brain works. For instance, we only recently learned that brain cells share information with virus-like capsules:

When Jason Shepherd first saw the structures under a microscope, he thought they looked like viruses. The problem was: he wasn’t studying viruses.

Shepherd studies a gene called Arc which is active in neurons, and plays a vital role in the brain. A mouse that’s born without Arc can’t learn or form new long-term memories. If it finds some cheese in a maze, it will have completely forgotten the right route the next day. “They can’t seem to respond or adapt to changes in their environment,” says Shepherd, who works at the University of Utah, and has been studying Arc for years. “Arc is really key to transducing the information from those experiences into changes in the brain.”

Despite its importance, Arc has been a very difficult gene to study. Scientists often work out what unusual genes do by comparing them to familiar ones with similar features—but Arc is one-of-a-kind. Other mammals have their own versions of Arc, as do birds, reptiles, and amphibians. But in each animal, Arc seems utterly unique—there’s no other gene quite like it. And Shepherd learned why when his team isolated the proteins that are made by Arc, and looked at them under a powerful microscope.

He saw that these Arc proteins assemble into hollow, spherical shells that look uncannily like viruses. “When we looked at them, we thought: What are these things?” says Shepherd. They reminded him of textbook pictures of HIV, and when he showed the images to HIV experts, they confirmed his suspicions. That, to put it bluntly, was a huge surprise. “Here was a brain gene that makes something that looks like a virus,” Shepherd says.

That’s not a coincidence. The team showed that Arc descends from an ancient group of genes called gypsy retrotransposons, which exist in the genomes of various animals, but can behave like their own independent entities.* They can make new copies of themselves, and paste those duplicates elsewhere in their host genomes. At some point, some of these genes gained the ability to enclose themselves in a shell of proteins and leave their host cells entirely. That was the origin of retroviruses—the virus family that includes HIV.

So, Arc genes are the evolutionary cousins of these viruses, which explains why they produce shells that look so similar. Specifically, Arc is closely related to a viral gene called gag, which retroviruses like HIV use to build the protein shells that enclose their genetic material. Other scientists had noticed this similarity before. In 2006, one team searched for human genes that look like gag, and they included Arc in their list of candidates. They never followed up on that hint, and “as neuroscientists, we never looked at the genomic papers so we didn’t find it until much later,” says Shepherd.

The similarities don’t end there. When genes are activated, the instructions encoded within their DNA are first transcribed into a related molecule called RNA. Shepherd’s colleague Elissa Pastuzyn showed that the Arc shells can enclose RNA and move it from one neuron to another. And that’s basically what retroviruses do—they use protein shells to protect their own RNA as it moves between cells in a host.

Comments

  1. Alrenous says:

    My theories on consciousness suggest the contents of those capsules are a key component of Descartes’ metonymic pineal gland.

  2. Kirk says:

    I’ve said it before, and I’ll say it again: We don’t know as much about biology as we think we do, and this just goes to prove that. HIV-like structures related to encoding memories… Wow. Makes you wonder, about “transmitted memory” between generations, and that whole supposed “racial memory” thing. This might indicate how such a mechanism would work…

  3. Auntiegrav says:

    Great article find! Thanks!

    I agree with Kirk. It’s always a hoot when someone pokes a hole in paradigms of “this works that way” and some dusty university department has to remodel all the lab…

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