A nuclear F-actin scaffold stabilizes ribonucleoprotein droplets against gravity in large cells

• Published in: Nature cell biology Vol. 15; no. 10; pp. 1253 - 1259
• Main Authors: Feric, Marina, Brangwynne, Clifford P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2013; Nature Publishing Group
• Subjects: 631/136/2434/1706; 631/80/128/1276; Actin; Actins - metabolism; Amphibians; Animals; Brownian motion; Cancer Research; Cell Biology; Cell Nucleus - metabolism; Cell Size; Cells; Developmental Biology; Eggs; Female; Gravitation; Humans; letter; Life Sciences; Microscopy, Confocal; Models, Biological; Nuclear Matrix - metabolism; Oocytes - cytology; Oocytes - growth & development; Oocytes - metabolism; Physiological aspects; Ribonucleoproteins; Ribonucleoproteins - metabolism; Stem Cells; Xenopus - metabolism; United States
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/ncb2830

Actin is abundant in the nuclei of oocytes but its role has been unclear. Feric and Brangwynne find that actin forms a network that prevents the sedimentation of RNA and protein bodies caused by gravitational forces. The size of a typical eukaryotic cell is of the order of ∼10 μm. However, some cell types grow to very large sizes, including oocytes (immature eggs) of organisms from humans to starfish. For example, oocytes of the frog Xenopus laevis grow to a diameter ≥1 mm. They have a correspondingly large nucleus (germinal vesicle) of ∼450 μm in diameter, which is similar to smaller somatic nuclei, but contains a significantly higher concentration of actin. The form and structure of this nuclear actin remain controversial, and its potential mechanical role within these large nuclei is unknown. Here, we use a microrheology and quantitative imaging approach to show that germinal vesicles contain an elastic F-actin scaffold that mechanically stabilizes these large nuclei against gravitational forces, which are usually considered negligible within cells. We find that on actin disruption, ribonucleoprotein droplets, including nucleoli and histone locus bodies, undergo gravitational sedimentation and fusion. We develop a model that reveals how gravity becomes an increasingly potent force as cells and their nuclei grow larger than ∼10 μm, explaining the requirement for a stabilizing nuclear F-actin scaffold in large Xenopus oocytes. All life forms are subject to gravity, and our results may have broad implications for cell growth and size control.