Control of cell growth and size

University Of California Santa Cruz, Santa Cruz CA

Investigators

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Abstract

The goal of our work is to discover fundamental mechanisms that control cell growth and size in all eukaryotic cells. Our work is focused on two key questions: 1. How do cells measure and limit growth to control cell size? In all cells, key cell cycle transitions occur only when sufficient growth has occurred. To enforce this critical dependency, cells must convert growth into a proportional signal that triggers cell cycle progression when it reaches a threshold. The mechanisms by which growth controls the cell cycle have remained deeply mysterious. We have discovered signals that are dependent upon growth, proportional to the extent of growth, and mechanistically linked to core cell cycle regulators, which suggests that they represent the long mysterious mechanisms that link cell cycle progression to cell growth. Growth-dependent signaling suggests a simple and broadly applicable solution to control of cell growth and size. 2. What are the signals that modulate cell growth and size? Observations reaching back over 60 years point to a close relationship between control of cell growth and size. Thus, growth rate is proportional to nutrient availability, cell size is proportional to growth rate, and growth rate is proportional to cell size. These relationships appear to hold across all orders of life, which suggest that they reflect fundamental principles, yet the underlying mechanisms have remained elusive. We discovered that signals arising from a conserved TORC2 signaling network enforce proportional relationships between nutrient availability, cell growth, and cell size. Our work suggests that TORC2-dependent signals that set growth rate also set the threshold amount of growth required for cell cycle progression, which would provide a simple but powerful mechanistic explanation for the proportional relationship between cell size and growth rate. Together, these new discoveries support transformational hypotheses that could broadly explain how cell growth and size are controlled. Our future work will test key hypotheses arising from our discoveries, while also carrying out mechanistic analysis to further map the remarkable signaling networks that control cell growth and size. All of the proteins that we have identified are highly conserved. Our work therefore leverages the experimental power of yeast to build a foundation for the discovery of mechanisms that control cell growth and size in all eukaryotic cells.