The discovery of a human homolog in C. elegans has provided new insights into diseases such as ALS (also known as Lou Gehrig's disease) and Alzheimer's. In a recent study published in Nature Communications, Dr. Emily Spaulding and Dr. Dustin Updike have identified a homolog of the well-known huma
has provided new insights into diseases such as ALS and, Dr. Emily Spaulding and Dr. Dustin Updike have identified a homolog of the well-known human protein Nucleolin inNucleolin has been associated with human neurodegenerative diseases and cancer. However, this new discovery challenges recent theories about the role that structures inside the nucleus may play in such disorders and provides a powerful new tool for studying the function of Nucleolin and its contribution to disease.
Super-resolution image of a nucleolus in a live, wild-type C. elegans nematode, left, shows well-organized architecture of interior condensates. At right, when a newly discovered coding gene called NUCL-1 is disrupted in a mutant worm, the architecture falls apart. Contrary to some thinking about the function of nucleolus substructures, both wild-type and mutant worms were healthy, developed normally, and retained fertility. Credit: Emily Spaulding, Ph.D.
Condensates form through liquid-to-liquid phase separation. Some imagine blobs of different densities forming inside a lava lamp, but exactly how this is achieved in living cells is unclear. Spaulding and Updike’s work shows that NUCL-1 is needed for phase separation in theSurprisingly, disrupting phase separation in the germline had no effect on health or fertility
Spaulding likens the nucleolus to a Tootsie Pop. “It’s got layers from the inside out,” she says. “Some proteins are localized to the innermost layer, and some proteins localize to the outermost layer. And each of these layers is thought to represent a step in ribosome biogenesis.”