5 TOR Signaling in Yeast: Temporal and Spatial Control of Cell Growth

Abstract

Cell growth is highly regulated. Cells respond to nutrients or other appropriate growth stimuli by up-regulating macromolecular synthesis, and thereby increasing in size. Conversely, cells respond to nutrient limitation or other types of stress by down-regulating macromolecular synthesis and enhancing turnover of excess mass. Thus, the control of cell growth involves balancing positive regulation of anabolic processes with negative regulation of catabolic processes. Growth is also controlled relative to cell division. In proliferating cells, growth is linked to the cell cycle such that cells generally double their mass before dividing. In other physiological contexts, such as load-induced muscle hypertrophy or growth factor–induced neuronal growth, cell growth can occur postmitotically. Furthermore, in addition to the temporal control of cell growth described above, cell growth can be subject to spatial constraints. For example, budding yeast and neurons grow in a polarized manner as a result of new mass being laid down only at one end of the cell. Finally, in multicellular organisms, growth of individual cells is controlled relative to overall body growth such that the organs constituting the organism are properly proportioned.

What are the mechanisms that mediate and integrate the many parameters of cell growth? In other words, what determines that a cell grows only at the right time and at the right place? Remarkably, the study of these mechanisms has been largely neglected, despite their clinical relevance and despite cell growth being, along with cell division and cell death, one of the most fundamental aspects of cell behavior.