Biology subjects

Kellogg, D.

Publications and source records attributed to Kellogg, D..

4 recordsLinked to original sources

bioRxiv2018

PP2A-Rts1 enforces a proportional relationship between cell size and growth rate

Cell size is proportional to growth rate. Thus, cells growing slowly in poor nutrients can be nearly half the size of cells growing rapidly in rich nutrients. The relationship between cell size and growth rate appears to hold across all orders of life, yet the underlying mechanisms are unknown. In budding yeast, most growth occurs during mitosis, and the proportional relationship between cell size and growth rate is therefore enforced primarily by modulating growth in mitosis. When growth is slow, the duration of mitosis is increased to allow more time for growth, yet the amount of growth required to complete mitosis is reduced, leading to birth of small daughter cells. Previous studies found that PP2A associated with the Rts1 regulatory subunit (PP2ARts1) works in a TORC2-dependent feedback loop that sets cell size and growth rate to match nutrient availability. However, it was unknown whether PP2ARts1 influences growth in mitosis. Here, we show that PP2ARts1 is required for the proportional relationship between cell size and growth rate during mitosis. Moreover, nutrients and PP2ARts1 influence the duration of mitosis, and thus the extent of growth in mitosis, via Wee1 and Pds1/securin, two conserved regulators of mitotic progression. Together, the data suggest a model in which the same global signals that set growth rate also set the critical amount of growth required for cell cycle progression, which would provide a simple mechanistic explanation for the proportional relationship between size and growth rate.

cell biology↗

bioRxiv2018

A conserved Lkb1 signaling axis modulates TORC2 signaling in budding yeast

Nutrient availability, growth rate and cell size are closely linked. For example, in budding yeast, the rate of cell growth is proportional to nutrient availability, cell size is proportional to growth rate, and growth rate is proportional to cell size. Thus, cells grow slowly in poor nutrients and are nearly half the size of cells growing in rich nutrients. Moreover, large cells grow faster than small cells. A signaling network that surrounds Tor kinase complex 2 (TORC2) plays an important role in enforcing these proportional relationships. Cells that lack components of the TORC2 network fail to modulate their growth rate or size in response to changes in nutrient availability. Here, we show that budding yeast homologs of the Lkb1 tumor suppressor kinase are required for normal modulation of TORC2 signaling and in response to changes in carbon source. Lkb1 kinases activate Snf1/AMPK to initiate transcription of genes required for utilization of poor carbon sources. However, Lkb1 influences TORC2 signaling via a novel pathway that is independent of Snf1/AMPK. Of the three Lkb1 homologs in budding yeast, Elm1 plays the most important role in modulating TORC2. Elm1 activates a pair of related kinases called Gin4 and Hsl1. Previous work found that loss of Gin4 and Hsl1 causes cells to undergo unrestrained growth during a prolonged mitotic arrest, which suggests that play a role in linking cell cycle progression to cell growth. We found that Gin4 and Hsl1 also control the TORC2 network. In addition, Gin4 and Hsl1 are themselves influenced by signals from the TORC2 network, consistent with previous work showing that the TORC2 network constitutes a feedback loop. Together, the data suggest a model in which the TORC2 network sets growth rate in response to carbon source, while also relaying signals via Gin4 and Hsl1 that set the critical amount of growth required for cell cycle progression. This kind of close linkage between control of cell growth and size would suggest a simple mechanistic explanation for the proportional relationship between cell size and growth rate.

cell biology↗

bioRxiv2017

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

The size of all cells, from bacteria to vertebrates, is proportional to the growth rate set by nutrient availability, but the underlying mechanisms are unknown. Here, we show that nutrients modulate TORC2 signaling, and that cell size is proportional to TORC2 signaling in budding yeast. The TORC2 network controls production of ceramide lipids, which play roles in signaling. We discovered that ceramide-dependent signals control both growth rate and cell size. Thus, cells that can not make ceramides fail to modulate their growth rate or size in response to changes in nutrients. PP2A associated with the Rts1 regulatory subunit (PP2ARts1) is embedded in a feedback loop that controls TORC2 signaling and plays an important role in mechanisms that modulate TORC2 signaling in response to nutrients. Together, the data suggest a model in which growth rate and cell size are mechanistically linked by ceramide-dependent signals arising from the TORC2 network.

cell biology↗

bioRxiv2017

A conserved signaling network monitors delivery of sphingolipids to the plasma membrane in budding yeast

In budding yeast, cell cycle progression and ribosome biogenesis are dependent upon plasma membrane growth, which ensures that events of cell growth are coordinated with each other and with the cell cycle. However, the signals that link the cell cycle and ribosome biogenesis to membrane growth are poorly understood. Here, we used proteome-wide mass spectrometry to systematically discover signals associated with membrane growth. The results suggest that membrane trafficking events required for membrane growth generate sphingolipid-dependent signals. A conserved signaling network plays an essential role in signaling by responding to delivery of sphingolipids to the plasma membrane. In addition, sphingolipid-dependent signals control phosphorylation of protein kinase C (Pkc1), which plays an essential role in the pathways that link the cell cycle and ribosome biogenesis to membrane growth. Together, these discoveries provide new clues to how growth-dependent signals control cell growth and the cell cycle.

cell biology↗