Keeping Cells in Shape: Movement in the Nucleolus

New research suggests that cellular health is maintained, in part, by two types of movement in the nucleolus. This dual motion within surrounding fluid, it reports, adds to our understanding of what contributes to healthy cellular function and points to how its disruption could affect human health.

“Nucleolar malfunction can lead to disease, including cancer,” says senior author Alexandra Zidovska of NYU. “Thus, understanding the processes responsible for the maintenance of nucleolar shape and motion might help in the creation of new diagnostics and therapies for certain human afflictions.”

Recently, it’s been discovered that some cellular compartments don’t have membranes, so researchers have investigated the forces that might hold them together. It’s been discovered that these compartments maintain their identity via a process called liquid–liquid phase separation, which has now been established as one of the key cellular organizing principles. In the present study, the researchers focused on the best-known example of this: the nucleolus.

“While the liquid-like nature of the nucleolus has been studied before, its relationship with the surrounding liquid is not known,” Zidovska explains. “This relationship is particularly intriguing considering the surrounding liquid—the nucleoplasm—contains the entire human genome.”

To better understand how the two fluids interact with each other, the scientists examined the motion and fusion of nucleoli in live human cells while monitoring their shape, size, and the smoothness of their surface. Their results showed two types of nucleolar pair movements: an unexpected correlated motion prior to their fusion and separate independent motion. Moreover, the team found that the smoothness of the nucleolar interface is susceptible to both changes in gene expression and the packing state of the genome.

“Nucleolus, the biggest droplet found inside the cell nucleus, serves a very important role in human aging, stress response, and general protein synthesis while existing in this special state,” Zidovska observes. “Because nucleoli are surrounded by fluid that contains our genome, their movement stirs genes around them. Consequently, because the genome in the surrounding fluid and nucleoli exist in a sensitive balance, a change in one can influence the other. Disrupting this state can potentially lead to disease.”

Image: Human cell nucleus with fluorescently labeled chromatin (green), nucleolar granular component (magenta) and nucleolar dense fibrillar component (blue). Image courtesy of Christina M. Caragine and Alexandra Zidovska, New York University.