Compositional adaptability in NPM1-SURF6 scaffolding networks enabled by dynamic switching of phase separation mechanisms. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Ferrolino, Mylene; Mitrea, Diana; Michael, J.; Kriwacki, Richard
• Is Part Of: Nature communications. Volume 9:Issue 1(2018)
• Page Start: 1
• Page End: 11
• Publication Date: 2018-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-018-07530-1
• Languages: English
• ISSNs: 2041-1723

Abstract

Abstract The nucleolus, the site for ribosome biogenesis contains hundreds of proteins and several types of RNA. The functions of many non-ribosomal nucleolar proteins are poorly understood, including Surfeit locus protein 6 (SURF6), an essential disordered protein with roles in ribosome biogenesis and cell proliferation. SURF6 co-localizes with Nucleophosmin (NPM1), a highly abundant protein that mediates the liquid-like features of the granular component region of the nucleolus through phase separation. Here, we show that electrostatically-driven interactions between disordered regions of NPM1 and SURF6 drive liquid-liquid phase separation. We demonstrate that co-existing heterotypic (NPM1-SURF6) and homotypic (NPM1-NPM1) scaffolding interactions within NPM1-SURF6 liquid-phase droplets dynamically and seamlessly interconvert in response to variations in molecular crowding and protein concentrations. We propose a mechanism wherein NPM1-dependent nucleolar scaffolds are modulated by non-ribosomal proteins through active rearrangements of interaction networks that can possibly contribute to the directionality of ribosomal biogenesis within the liquid-like nucleolus. The nucleolus is a membrane-less organelle and both Nucleophosmin (NPM1) and Surfeit locus protein 6 (SURF6) are abundant proteins within the nucleolus. Here the authors employ biophysical methods to study the properties of NPM1-S6N droplets and provide insights into the role of SURF6 in maintaining and modulating the liquid-like structure of the nucleolus.