This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Unexpectedly, a kind of protein that is usually linked with diseases in the brain may play a vital role in semen, helping shepherd genetic material into sperm cells, scientists at Columbia's Zuckerman Institute report in the journal Molecular Cell. These findings raise the possibility that these proteins, known as amyloids, may one day help improve gene-editing technologies such as CRISPR.
"This is wild biology," said senior author on the paper Anthony Fitzpatrick, Ph.D., a principal investigator at Columbia's Zuckerman Institute. "Amyloids are most often thought of as a hallmark of Alzheimer's, Parkinson's and other neurodegenerative diseases in the brain, but they also have functional roles throughout the body and keep turning up in unexpected places." This unusual project had an even more unusual starting point: the virus HIV. Previous research had found that amyloid fibrils present in semen could help HIV enter cells in the reproductive tract, explained William Mallen, Ph.D., the study's lead author, who conducted this research while he was a doctoral student in the Fitzpatrick lab.
Fitzpatrick, an expert on amyloids in brain research, wondered if those fibrils could also help materials naturally in the body enter sperm: specifically, the genetic molecule RNA, which helps turn instructions encoded in DNA into protein molecules. Scientists knew that seminal fluid contains lots of small RNAs, thought to play a major role in what genes are active in developing embryos. But how this RNA gets chaperoned from seminal fluid into sperm to influence the embryo—that was a mystery.
The potential link the researchers made between amyloids and RNA was how HIV uses RNA as its genetic material, as is true with roughly half of all known viruses. Since amyloids could help HIV enter cells, maybe they could do so with RNA in general. Amyloids seemed promising escorts for RNA, in part because these amyloids are positively charged, while RNA is negatively charged, and for molecules, like magnets, opposites attract.
Using fluorescent labels on both kinds of molecules, Mallen found that they do bind together and speculated that the amyloids have a protective function. While RNA is quite fragile, amyloids are exceptionally durable, so packaging RNA in an amyloid scaffold could help the genetic molecules survive harsh conditions. The researchers next analyzed sperm using cryo-electron tomography (cryo-ET), which fires beams of electrons at frozen specimens to create 3D images of the samples.
Cryo-ET, the most powerful form of microscopy used in biology today, can achieve near-atomic-level resolution. Using amyloid proteins labeled with flecks of gold, the scientists confirmed these molecules could in fact enter sperm, and not just, say, embed onto their surfaces. "Seeing those amyloid fibers inside sperm cells was just so extraordinary to me," said Mallen, who is now in medical school at the University of Vermont.
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