Coexisting Liquid Phases Underlie Nucleolar Subcompartments
The nucleolus – the cell’s sub-nuclear center for ribosome biogenesis – displays two extremely interesting yet apparently confounding behaviors. Extensive imaging studies have demonstrated that the nucleolus contains (at least) three distinct regions, believed to be responsible for different stages of ribosome assembly and maturation. Simultaneously, the nucleolus has been demonstrated to behave as a liquid, undergoing fusion, wetting, and gravitational sedimentation in the absence of the nuclear actin network. How can can apparent liquid-like properties be reconciled with well-defined spatial organization?
Recent work by Feric & Vaidya et al. sought to answer this question using a combination of in vivo, in vitro, and in silico approaches to tease apart the physical chemistry that might underlie these observations. IDRs identified in several key proteins were shown to have distinct preferences for one another and for the solution environment, facilitating organized and predictable spatial assembly. Importantly, the interplay between ordered domains and these IDRs was crucial for the spatial assembly, despite the fact these ordered domains were unable to undergo phase separation in isolation. The authors demonstrate the underlying principles elucidated through this work using numerical simulations that reproduce the in vitro and in vivo data, as well as constructing a model system using water, Crisco oil and silicone oil that demonstrates similar spatial behaviour. The implications from this work are substantial: it seems likely - if not inevitable - that other membrane-less organelles will display similar spatial organization as a consequence of the relative miscibility of their constitutive protein components. Such organization affords the construction of specific sub-organelle “bioreactors” (sub-regions consisting of a specific protein composition), in principle giving cells a way to organize complex and potentially hazardous processes in a manner that reduces side-reactions and maximizes enzymatic efficiency.
Dr. Cliff Brangwynne is an assistant professor in the Department of Chemical and Biological Engineering at Princeton University, New Jersey.