Protein kinase Gin4 negatively regulates flippase function and controls plasma membrane asymmetry

Roelants, Françoise M.; Su, Brooke M.; Wulffen, Joachim von; Ramachandran, Subramaniam; Sartorel, Elodie; Trott, Amy; Thorner, Jeremy

doi:10.1085/jgp.1453oia6

Cited by 4 publications

(4 citation statements)

References 40 publications

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“…Since shifts in the electrophoretic mobility of Ypk1 are due to the Fpk1/2 kinases (Roelants et al 2010), the data suggest that Fpk1/2 have reduced activity in cells that lack Elm1 or the Gin4-related kinases. In contrast, a previous study found evidence that Gin4, but not Hsl1 or Kcc4, inhibits Fpk1/2 (Roelants et al 2015). There are significant technical differences in experimental approaches that could explain the different conclusions.…”

Section: Gin4-related Kinases Are Required For Nutrient Modulation Ofmentioning

confidence: 75%

Modulation of TORC2 Signaling by a Conserved Lkb1 Signaling Axis in Budding Yeast

et al. 2018

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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 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 they 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.3

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Section: Gin4-related Kinases Are Required For Nutrient Modulation Ofmentioning

confidence: 75%

Modulation of TORC2 Signaling by a Conserved Lkb1 Signaling Axis in Budding Yeast

et al. 2018

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“…Septins are closely apposed to the plasma membrane, and this may restrict the passage of integral membrane proteins of a sufficient size. Alternatively, or in addition, septins or septinbinding proteins may recruit, modify, or maintain a pool of specific lipids leading to a selectively permeable barrier that operates based on lipid preferences of the impacted proteins (8,71). The diffusion barrier property of septin assemblies was noticed, and has been most studied at the yeast mother-bud neck where septins are thought to restrict diffusion of membrane-associated proteins and lipids between mother and bud, in effect maintaining asymmetrically distributed membrane proteins (72,73).…”

Section: Function Of Higher-order Structures At the Cell Cortexmentioning

confidence: 99%

Septin Form and Function at the Cell Cortex

Bridges

Gladfelter

2015

Journal of Biological Chemistry

131

138

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Septins are a conserved family of cytoskeletal GTP-binding proteins that function in cytokinesis, cell polarity, and membrane remodeling in many eukaryotic cell types (1, 2). To contribute to these diverse process, septins polymerize into filaments and higher-order structures that organize the cell cortex into domains that are tightly controlled in time and/or space (3). Higher-order septin structures act to recruit and/or integrate protein networks at specific locations, an example being contractile ring components in cell division (4 -7). In addition, septins are thought to alter lateral diffusion of proteins embedded in the plasma and endoplasmic reticulum (ER) 2 membranes and may influence local lipid composition (8 -10). In addition to membrane association, septins interact with, respond to, and organize the actin and microtubule cytoskeletons (11). Although septins were discovered by Hartwell, Pringle, and colleagues (12) in cell division cycle screens decades ago, understanding of septins has lagged behind other cytoskeletal systems. Recent biochemical, structural, and biophysical approaches, however, have made septins highly tractable and brought about exciting advances. Despite this recent progress, many fundamental questions remain in the septin field, in particular, the mechanisms by which septins associate with and influence the cell cortex.

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“…Cells may monitor defects as cell wall stress via activation of the cell wall integrity pathway (Philip and Levin, 2001) or they may monitor disruptions to the plasma membrane (Kono et al, 2012) or they may monitor a yet unidentified morphological change. Interestingly, decreasing lipid flippase function at the plasma membrane during cytokinesis was shown to suppress the poor growth of septation mutants (Roelants et al, 2015) suggesting that plasma membrane composition changes during cytokinesis could be involved.…”

Section: A Checkpoint That Monitors Cytoplasmic Separationmentioning

confidence: 99%

A cell separation checkpoint that enforces the proper order of late cytokinetic events

Brace¹,

Doerfler²,

Weiss³

2018

Preprint

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List of Abbreviations:Actomyosin ring (AMR); Primary septum (PS); Secondary septum (SS); Cyclin dependent kinase (CDK); Auxin inducible degron (AID); Immunoprecipitation (IP); Mitotic Exit Network (MEN); Regulation of Ace2 and Morphogenesis network (RAM) SummaryEukaryotic cell division requires sequence dependency relationships in which late processes commence only after early ones are appropriately completed. We have discovered a system that blocks late events of cytokinesis until early ones are successfully accomplished. In budding yeast, cytokinetic actomyosin ring contraction and membrane ingression are coupled with deposition of an extracellular septum that is destroyed immediately after its completion by secreted enzymes. We find this secretion event is linked to septum completion and forestalled when the process is slowed. Delay of septum destruction requires Fir1, an intrinsically disordered protein localized to the cytokinesis site that is degraded upon septum completion but stabilized when septation is aberrant. Fir1 appears to protect cytokinesis in part by inhibiting a separation-specific exocytosis function of the NDR/LATS kinase Cbk1, a key component of a "hippo" signaling pathway that induces mother-daughter separation. We term this system "enforcement of cytokinesis order" (ECO), a checkpoint ensuring proper temporal sequence of mechanistically incompatible processes of cytokinesis.Eukaryotic cells undergo dramatic reorganization at the end of mitosis, producing two cells from one through the processes of cytokinesis. This division requires execution of mechanistically diverse events in an unvarying and often rapid sequence, in which late processes are not initiated until early ones are effectively completed. Specification of the division site and assembly of cytokinetic structures precedes the mechanical and regulatory events of actomyosin ring (AMR) constriction and membrane ingression; this is followed by disassembly of cytokinetic machinery, cessation of cytokinetic membrane trafficking, and abscission of the divided cells (

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Protein kinase Gin4 negatively regulates flippase function and controls plasma membrane asymmetry

Cited by 4 publications

References 40 publications

Modulation of TORC2 Signaling by a Conserved Lkb1 Signaling Axis in Budding Yeast

Modulation of TORC2 Signaling by a Conserved Lkb1 Signaling Axis in Budding Yeast

Septin Form and Function at the Cell Cortex

A cell separation checkpoint that enforces the proper order of late cytokinetic events

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