TY - JOUR
T1 - Inverse size scaling of the nucleolus by a concentration-dependent phase transition
AU - Weber, Stephanie C.
AU - Brangwynne, Clifford P.
N1 - Funding Information:
We thank Joel Berry, Chase Broedersz, Mikko Haataja, Tony Hyman, Sravanti Uppaluri, and members of the C.P.B. laboratory for helpful discussions; Stephan Thiberge and Evangelos Gatzogiannis for imaging advice; and Nilesh Vaidya for protein purification. Some strains were provided by the CGC, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). This work was supported by the NIH Director’s New Innovator Award (1DP2GM105437-01), the Searle Scholars Program, an NSF CAREER Award (1253035), and a Damon Runyon Postdoctoral Fellowship (S.C.W.).
Publisher Copyright:
© 2015 Elsevier Ltd All rights reserved.
PY - 2015/3/2
Y1 - 2015/3/2
N2 - Just as organ size typically increases with body size, the size of intracellular structures changes as cells grow and divide. Indeed, many organelles, such as the nucleus [1, 2], mitochondria [3], mitotic spindle [4, 5], and centrosome [6], exhibit size scaling, a phenomenon in which organelle size depends linearly on cell size. However, the mechanisms of organelle size scaling remain unclear. Here, we show that the size of the nucleolus, a membraneless organelle important for cell-size homeostasis [7], is coupled to cell size by an intracellular phase transition. We find that nucleolar size directly scales with cell size in early C. elegans embryos. Surprisingly, however, when embryo size is altered, we observe inverse scaling: nucleolar size increases in small cells and decreases in large cells. We demonstrate that this seemingly contradictory result arises from maternal loading of a fixed number rather than a fixed concentration of nucleolar components, which condense into nucleoli only above a threshold concentration. Our results suggest that the physics of phase transitions can dictate whether an organelle assembles, and, if so, its size, providing a mechanistic link between organelle assembly and cell size. Since the nucleolus is known to play a key role in cell growth, this biophysical readout of cell size could provide a novel feedback mechanism for growth control.
AB - Just as organ size typically increases with body size, the size of intracellular structures changes as cells grow and divide. Indeed, many organelles, such as the nucleus [1, 2], mitochondria [3], mitotic spindle [4, 5], and centrosome [6], exhibit size scaling, a phenomenon in which organelle size depends linearly on cell size. However, the mechanisms of organelle size scaling remain unclear. Here, we show that the size of the nucleolus, a membraneless organelle important for cell-size homeostasis [7], is coupled to cell size by an intracellular phase transition. We find that nucleolar size directly scales with cell size in early C. elegans embryos. Surprisingly, however, when embryo size is altered, we observe inverse scaling: nucleolar size increases in small cells and decreases in large cells. We demonstrate that this seemingly contradictory result arises from maternal loading of a fixed number rather than a fixed concentration of nucleolar components, which condense into nucleoli only above a threshold concentration. Our results suggest that the physics of phase transitions can dictate whether an organelle assembles, and, if so, its size, providing a mechanistic link between organelle assembly and cell size. Since the nucleolus is known to play a key role in cell growth, this biophysical readout of cell size could provide a novel feedback mechanism for growth control.
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U2 - 10.1016/j.cub.2015.01.012
DO - 10.1016/j.cub.2015.01.012
M3 - Article
C2 - 25702583
AN - SCOPUS:84924804206
SN - 0960-9822
VL - 25
SP - 641
EP - 646
JO - Current Biology
JF - Current Biology
IS - 5
ER -