Loss of growth homeostasis by genetic decoupling of cell division from biomass growth: implication for size control mechanisms

Molecular Systems Biology

Hannah Schmidt-Glenewinkel¹ 

[1] Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel

关键词: glucose signalling;    cell size control;    external vs. internal signalling;    microfluidics;   

DOI  :  10.15252/msb.20145513

来源: Wiley

【 摘 要 】

Abstract

Growing cells adjust their division time with biomass accumulation to maintain growth homeostasis. Size control mechanisms, such as the size checkpoint, provide an inherent coupling of growth and division by gating certain cell cycle transitions based on cell size. We describe genetic manipulations that decouple cell division from cell size, leading to the loss of growth homeostasis, with cells becoming progressively smaller or progressively larger until arresting. This was achieved by modulating glucose influx independently of external glucose. Division rate followed glucose influx, while volume growth was largely defined by external glucose. Therefore, the coordination of size and division observed in wild-type cells reflects tuning of two parallel processes, which is only refined by an inherent feedback-dependent coupling. We present a class of size control models explaining the observed breakdowns of growth homeostasis.

Synopsis

Live microscopy of individual cells growing in conditions that decouple nutrient sensing from nutrient influx reveals independent regulation of biomass accumulation and cell division. Two distinct types of arrest are described with implications for models of cell size control.

• We use genetic manipulations that enable modulating glucose influx independently of external glucose to interrogate the coordination of biomass accumulation and cell division cycle observed under normal conditions.
• Cell size follows external glucose, whereas division rate is controlled by glucose influx, leading to the loss of growth homeostasis.
• Cells continuously increase or decrease their size until arresting, challenging existing models of cell size control.

【 授权许可】

CC BY   
© 2014 The Authors. Published under the terms of the CC BY 4.0 license

Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.