Ypk1 and Ypk2 kinases maintain Rho1 at the plasma membrane by flippase-dependent lipid remodeling after membrane stresses

Hatakeyama, Riko; Kono, Keita; Yoshida, Satoshi

doi:10.1242/jcs.198382

Cited by 25 publications

(18 citation statements)

References 74 publications

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“…However, previous studies found that defects caused by inhibition of serine palmitoyltransferase can be suppressed by increased activity of Pkc1, which suggests that inhibition of sphingolipid synthesis leads to a failure to fully activate Pkc1 (Friant et al, 2000;Olson et al, 2015). There is also evidence that sphingolipids promote Pkc1 activity via activation of the Rho1 GTPase, although the underlying mechanisms remain largely unknown (Niles and Powers, 2014;Olson et al, 2015;Hatakeyama et al, 2017). Together, the data suggest that sphingolipids promote Pkc1 activation, potentially by promoting Pkc1 phosphorylation.…”

Section: Inactivation Of Ypk1/2 Causes a Failure In Pkc1 Phosphorylatmentioning

confidence: 82%

“…Extensive work has shown that TORC2 and Ypk1/2, as well as their surrounding signaling network, play roles in controlling cell growth, lipid synthesis and cell cycle progression. In addition, multiple previous studies have suggested that TORC2 and Ypk1/2 control Rho1/Pkc1 signaling (Helliwell et al, 1998;Roelants et al, 2002;Schmelzle et al, 2002;Kamada et al, 2005;Niles and Powers, 2014;Hatakeyama et al, 2017). Figure 1A provides an overview of the TORC2-Ypk1/2 network, with proteins identified by mass spectrometry highlighted in red.…”

Section: Blocking Membrane Traffic Disrupts a Signaling Network That mentioning

confidence: 99%

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

Clarke

Dephoure

Horecka

et al. 2017

Preprint

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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.

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Section: Inactivation Of Ypk1/2 Causes a Failure In Pkc1 Phosphorylatmentioning

confidence: 82%

Section: Blocking Membrane Traffic Disrupts a Signaling Network That mentioning

confidence: 99%

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

Clarke

Dephoure

Horecka

et al. 2017

Preprint

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“…First, among the suppressors of the temperature-sensitivity of both lst8∆ and tor2-21 ts cells were loss-of-function mutations in the gene for the Rho1 GAP Sac7, suggesting that increasing the steady-state supply of Rho1-GTP may, in turn, upregulate Pkc1 function, which is then responsible for the rescue [ 291 ]. Second, the PM lipid most responsible for PM recruitment of Rho1 under normal conditions is PtdIns4,5P2 [ 221 ]; however, it has been reported that, under conditions of membrane stress (hypotonic shock and myriocin treatment), PM PtdIns4,5P2 is acutely degraded, but that Rho1 is nevertheless retained at the PM because activation of TORC2-Ypk1 signaling somehow causes an alternative acidic glycerophospholipid—namely, PtdSer—to be accumulated in the inner leaflet of the PM [ 292 ]. It is further claimed [ 292 ] that the observed increase in PtdSer somehow arises from preventing Fpk1-mediated stimulation of the Lem3-dependent flippases Dnf1 and Dnf2 [ 52 , 284 ].…”

Section: Cross-talk Between Ypk1- and Pkc1-dependent Signalingmentioning

confidence: 99%

The TORC2‐Dependent Signaling Network in the Yeast Saccharomyces cerevisiae

et al. 2017

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To grow, eukaryotic cells must expand by inserting glycerolipids, sphingolipids, sterols, and proteins into their plasma membrane, and maintain the proper levels and bilayer distribution. A fungal cell must coordinate growth with enlargement of its cell wall. In Saccharomyces cerevisiae, a plasma membrane-localized protein kinase complex, Target of Rapamicin (TOR) complex-2 (TORC2) (mammalian ortholog is mTORC2), serves as a sensor and master regulator of these plasma membrane- and cell wall-associated events by directly phosphorylating and thereby stimulating the activity of two types of effector protein kinases: Ypk1 (mammalian ortholog is SGK1), along with a paralog (Ypk2); and, Pkc1 (mammalian ortholog is PKN2/PRK2). Ypk1 is a central regulator of pathways and processes required for plasma membrane lipid and protein homeostasis, and requires phosphorylation on its T-loop by eisosome-associated protein kinase Pkh1 (mammalian ortholog is PDK1) and a paralog (Pkh2). For cell survival under various stresses, Ypk1 function requires TORC2-mediated phosphorylation at multiple sites near its C terminus. Pkc1 controls diverse processes, especially cell wall synthesis and integrity. Pkc1 is also regulated by Pkh1- and TORC2-dependent phosphorylation, but, in addition, by interaction with Rho1-GTP and lipids phosphatidylserine (PtdSer) and diacylglycerol (DAG). We also describe here what is currently known about the downstream substrates modulated by Ypk1-mediated and Pkc1-mediated phosphorylation.

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“…GFP-tagged Rho1 has been reported to localize at the plasma membranes and endomembrane including vacuolar membranes, in which PtdIns(3,5)P 2 is abundant (57). A recent study reported that the C terminus of Rho1 has the ability to bind to some anionic lipids including PtdIns(3,5)P 2 in vitro (58). These findings imply that PtdIns(3,5)P 2 is involved in the MG-induced activation of the Pkc1-Mpk1 MAPK cascade via Rho1.…”

Section: Role Of Ptdins(35)p 2 In Mg-induced Mpk1 Phosphorylationmentioning

confidence: 99%

Phosphatidylinositol 3,5-bisphosphate is involved in methylglyoxal-induced activation of the Mpk1 mitogen-activated protein kinase cascade in Saccharomyces cerevisiae

Nomura

Maeta

Inoue

2017

Journal of Biological Chemistry

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Methylglyoxal (MG) is a natural metabolite derived from glycolysis, and this 2-oxoaldehyde has been implicated in some diseases including diabetes. However, the physiological significance of MG for cellular functions is yet to be fully elucidated. We previously reported that MG activates the Mpk1 (MAPK) cascade in the yeast To gain further insights into the cellular functions and responses to MG, we herein screened yeast-deletion mutant collections for susceptibility to MG. We found that mutants defective in the synthesis of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P) are more susceptible to MG. PtdIns(3,5)P levels increased following MG treatment, and vacuolar morphology concomitantly changed to a single swollen shape. MG activated the Pkc1-Mpk1 MAPK cascade in which a small GTPase Rho1 plays a crucial role, and the MG-induced phosphorylation of Mpk1 was impaired in mutants defective in the PtdIns(3,5)P biosynthetic pathway. Of note, heat shock-induced stress also provoked Mpk1 phosphorylation in a Rho1-dependent manner; however, PtdIns(3,5)P was dispensable for the heat shock-stimulated activation of this signaling pathway. Our results suggest that PtdIns(3,5)P is specifically involved in the MG-induced activation of the Mpk1 MAPK cascade and in the cellular adaptation to MG-induced stress.

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Ypk1 and Ypk2 kinases maintain Rho1 at the plasma membrane by flippase-dependent lipid remodeling after membrane stresses

Cited by 25 publications

References 74 publications

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

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

The TORC2‐Dependent Signaling Network in the Yeast Saccharomyces cerevisiae

Phosphatidylinositol 3,5-bisphosphate is involved in methylglyoxal-induced activation of the Mpk1 mitogen-activated protein kinase cascade in Saccharomyces cerevisiae

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