Thursday, January 11, 2018

AN INFECTIOUS IDEA -- A VIRUS-LIKE PROTEIN MAY BE CRUCIAL TO LEARNING AND MEMORY

We've all heard the phrase, "an infectious idea." It turns out that this may not just be a metaphor--new research has revealed that a virus-like protein in all of our brains may be vital for learning and memory.

"If it looks like a duck and quacks like a duck," the saying goes, "it probably is a duck." So, no matter how surprising it is, finding a crucial protein in the brain that looks like a virus and acts like a virus raises the intriguing possibility that our ability to learn and remember may stem from a chance infection of some ancestral four-legged creature by a retrovirus 350 to 400 million years ago.

The protein in question is called Arc. It's found in animals as different as flies, mice and humans. It's been known for some time that Arc is important for learning and memory. Mice lacking Arc forget what they've learned within 24 hours, and lack the kind of brain plasticity that lets young animals, most notably human children, soak up new information quickly and easily. Arc continues to be important for learning and memory throughout life, and impaired Arc functioning is associated with autism, amnesia and Alzheimer's disease.

Arc (long purple proteins inside the perimeter of the vesicle) can encapsulate and deliver its own genetic material to brain cells (light green branching blobs) in a manner similar to the way in which viruses infect host cells.  
Credit: Jacobo Lopez, Yi-Chu Su, Hugo Vaca

Jason Shepherd, a neuroscientist at the University of Utah, and his colleagues first suspected that something was different about Arc when they found that the protein self-assembles into structures called capsids that look like a lunar lander or the HIV retrovirus. Intrigued, they found that not only can the Arc capsid jump from cell to cell like a virus, it also transfers its own genetic material in the form of messenger RNA into the new cell.

Learning takes place when interconnected brain cells are activated at the same time. Intriguingly, the researchers found that when neurons "infected" by Arc are activated, they release newly minted Arc capsids. This suggests that the transfer of this virus-lilke protein from cell to cell may be a previously unknown and unsuspected mechanism for learning and memory.

Neuron expressing Arc and transferring it to other neurons
Credit: Elissa Pastuzyn 

“We went into this line of research knowing that Arc was special in many ways," says the study’s lead author, postdoctoral fellow Elissa Pastuzyn. "But when we discovered that Arc was able to mediate cell-to-cell transport of RNA, we were floored. No other non-viral protein that we know of acts in this way.”

Geneticists have been able to trace back the history of the Arc proteins found in all mammals. Sometime between 350 and 400 million years ago, a primitive four-limbed creature, or tetrapod, was infected by a retrovirus that left some of its genetic material in the animal's DNA. That chance addition to the mammalian genetic code has apparently proven extremely useful, perhaps laying the groundwork for the success of our mammalian ancestors, and even for our remarkable capacity for learning and remembering.

REA
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You can read more about this research at this URL.

The scientific article describing this research can be found in Cell, January 11, 2018.

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