UC Santa Cruz

All cells big and small possess the ability to grow. Despite this, cells in a given population have very similar sizes, suggesting that they must possess inherent mechanisms that determine how much they grow and when to stop growing. Growth homeostasis is especially important at the time of cell division to ensure that daughter cells are the same size as their mother. Coordination of cell growth with cell division is a universal phenomenon in all orders of life; however, the mechanisms that measure cell growth have remained elusive. Moreover, it is not clear what cells “measure” as a readout of cell growth. In the following chapters, I will provide evidence that protein kinases measure signaling lipids deposited at sites of growth to gauge the extent of cell growth in Saccharomyces cerevisiae and then relay growth-dependent signals to relevant cell cycle control proteins to link cell cycle progression to cell growth.

In chapters 2 and 3, I present evidence that suggests that Gin4 and Hsl1 kinases are essential for coordination of cell cycle progression with cell growth. Inactivation of these kinases causes cells to behave as if they cannot detect that growth has occurred, which results in strong growth defects. Moreover, the activation of Gin4/Hsl1 is dependent on and proportional to growth. The data further suggest that activation of Gin4 by signaling lipids is the basis of measuring cell growth.

In chapter 4, I focus on the kinase Pkc1 (protein kinase C) and its role as a growth sensor for polar bud growth. Pkc1 is maximally active at G2 and is well-positioned to detect bud growth. It is activated by Rho1 and together they interact with the phosphatase PP2ACdc55 to link mitotic entry to polar cell growth.