The duration of mitosis and daughter cell size are modulated by nutrients in budding yeast

Abstract

The size of nearly all cells is modulated by nutrients. Thus, cells growing in poor nutrients can be nearly half the size of cells in rich nutrients. In budding yeast, cell size is thought to be controlled almost entirely by a mechanism that delays cell cycle entry until sufficient growth has occurred in G1 phase. Here, we show that most growth of a new daughter cell occurs in mitosis. When the rate of growth is slowed by poor nutrients, the duration of mitosis is increased, which suggests that cells compensate for slow growth in mitosis by increasing the duration of growth. The amount of growth required to complete mitosis is reduced in poor nutrients, leading to a large reduction in cell size. Together, these observations suggest that mechanisms that control the extent of growth in mitosis play a major role in cell size control in budding yeast.

Cell size and growth rate are modulated by TORC2-dependent signals

“…In previous studies we discovered that PP2A Rts1 is required for nutrient modulation of cell size [2,18]. Here, we found that PP2A Rts1 controls signaling in the TORC2 network, and that signals from the TORC2 network are required for normal control of cell size.…”

“…In previous work, we discovered that PP2A Rts1 , a form of PP2A associated with the Rts1 regulatory subunit, is required for nutrient modulation of cell size [18]. In addition, inactivation of PP2A Rts1 abolishes the linear relationship between cell size and growth rate [2]. Together, these observations suggest that PP2A Rts1 could play an important role in mechanisms that control cell growth and size.…”

“…For example, when cells are shifted from poor to rich carbon in early G1 phase, the duration of G1 phase is dramatically increased compared to cells that remain in poor carbon. In contrast, cells that have been growing continuously in rich carbon have a much shorter G1 phase than cells growing in poor carbon, which is thought to be a consequence of cells in poor carbon being born at a smaller size and therefore having to undergo more growth in G1 to reach a threshold amount of growth for cell cycle entry [2,51,52]. Thus, the duration of growth in G1 phase is most closely correlated with the initial size of the cell and its rate of growth, rather than the carbon source, which argues against nutrient-modulated timer models.…”

“…The idea that signals originating in the TORC2 network coordinately control growth rate and size would explain why loss of PP2A Rts1 disrupts TORC2 signaling, as well as the normal relationship between growth rate and cell size [2,18]. An alternative model is that the close relationship between growth rate and size is the consequence of mechanisms that read growth rate and set cell size accordingly.…”

“…Indeed, there is evidence for a close relationship between cell growth and size. For example, in budding yeast, cell size at all cell cycle transitions is linearly proportional to the growth rate during the previous growth interval [1,2]. Moreover, the size of cells, from bacteria to vertebrates, is proportional to the growth rate set by nutrients [3][4][5][6][7].…”