If prizes were awarded for weirdness, the agents that cause illnesses like mad cow disease would surely take top honors. What could be stranger than an infectious particle that makes animals stumble and scratch themselves viciously? What could be more unsettling than an entity that can move between species, and cause symptoms years after it infects its victims? And what could be more freakish than a disease-causing agent that seems to be pure protein, with no genes to transmit its biological information?
Until recently, researchers thought these infectious proteins, called prions, were indeed exceptional molecules, whose sole effect was to cause rare diseases. But prions may not be as rare, or even as sinister, as once thought. Some fungi harbor several kinds of prion proteins. And thanks to their discovery, researchers have been able to examine prions in greater detail than ever before. The new information is helping them develop ideas for future therapies. It is also revealing how prions are not always harmful, and how sometimes they even help cells stay healthy.
Proving that prions can cause and transmit disease has been a challenge that has plagued researchers for the past 20 years. Skeptics have suggested that viruses could be the true culprits behind the so-called prion diseases. Although scientists have yet to prove that these illnesses are caused by prions alone, fungi have now offered definitive evidence that prions can cause heritable alterations in cells. In fact, researchers have even created artificial prions by attaching a piece of a fungal prion protein to a normal rat protein. It is now clear that by changing their own shape and inducing shape changes in other proteins, prions can transmit biological information as surely as a gene, without the help of DNA or any other molecule.
Fungi are also revealing the means by which prions accomplish such a feat. Proteins called chaperones, which coordinate the normal folding of proteins, seem to affect the behavior of prions. By tweaking the amounts of certain chaperones in fungi, researchers can prevent or promote prion proteins from adopting their transmissible state. Such findings may someday lead to the development of new therapies -- not only for the traditional prion diseases, but for other illnesses that also involve abnormal protein structures, such as Alzheimer*s disease.
Not all prions, however, are linked to disease. Cells may require prions for some of their normal, everyday functions. When some types of fungal colonies grow close together, they fuse with one another to share food. But they're selective about it. To reduce their risk of viral infection, some fungi fuse only with genetically related neighbors. Kindred colonies are more likely to carry similar viruses. So by sticking to their own kind, these colonies protect themselves from exposure to new, potentially dangerous viruses. One of the key players behind this judicious management of promiscuity is Het-s, a prion protein. When Het-s is in its transmissible, prion form, it prevents fusion with unrelated colonies.
So far, Het-s is the sole example of a beneficial prion. But the search for prions in normal processes has just begun. Some researchers anticipate discovering other useful prion behaviors, perhaps even in mammals. Mad cows and promiscuous fungi may be merely the tip of the iceberg.