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Sng1 associates with Nce102 to regulate the yeast Pkh–Ypk signalling module in response to sphingolipid status

Sara García-Marqués 1 Francisca Randez-Gil 1 Sébastien Dupont 2 Elena Garre 3, 1 Jose A. Prieto 1, * 
* Auteur correspondant
2 PMB - Procédés Microbiologiques et Biotechnologiques
PAM - Procédés Alimentaires et Microbiologiques, PAM - Procédés Alimentaires et Microbiologiques [Dijon]
Abstract : All cells are delimited by biological membranes, which are consequently a primary target of stress-induced damage. Cold alters membrane functionality by decreasing lipid fluidity and the activity of membrane proteins. In Saccharomyces cerevisiae, evidence links sphingolipid homeostasis and membrane phospholipid asymmetry to the activity of the Ypk1/2 proteins, the yeast orthologous of the mammalian SGK1-3 kinases. Their regulation is mediated by different protein kinases, including the PDK1 orthologous Pkh1/2p, and requires the function of protein effectors, among them Nce102p, a component of the sphingolipid sensor machinery. Nevertheless, the mechanisms and the actors involved in Pkh/Ypk regulation remain poorly defined. Here, we demonstrate that Sng1, a transmembrane protein, is an effector of the Pkh/Ypk module and identify the phospholipid asymmetry as key for yeast cold adaptation. Overexpression of SNG1 impairs phospholipid flipping, reduces reactive oxygen species (ROS) and improves, in a Pkh-dependent manner, yeast growth in myriocin-treated cells, suggesting that excess Sng1p stimulates the Pkh/Ypk signalling. Furthermore, we link these effects to the association of Sng1p with Nce102p. Indeed, we found that Sng1p interacts with Nce102p both physically and genetically. Moreover, mutant nce102 Delta sng1 Delta cells show features of impaired Pkh/Ypk signalling, including increased ROS accumulation, reduced life span and defects in Pkh/Ypk-controlled regulatory pathways. Finally, myriocin-induced hyperphosphorylation of Ypk1p and Orm2p, which controls sphingolipid homeostasis, does not occur in nce102 Delta sng1 Delta, cells. Hence, both Nce102p and Sng1p participate in a regulatory circuit that controls the activity of the Pkh/Ypk module and their function is required in response to sphingolipid status.
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Soumis le : mardi 18 avril 2017 - 09:41:42
Dernière modification le : lundi 21 novembre 2022 - 03:53:26

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Sara García-Marqués, Francisca Randez-Gil, Sébastien Dupont, Elena Garre, Jose A. Prieto. Sng1 associates with Nce102 to regulate the yeast Pkh–Ypk signalling module in response to sphingolipid status. Biochimica et Biophysica Acta - Molecular Cell Research, 2016, 1863 (6), pp.1319 - 1333. ⟨10.1016/j.bbamcr.2016.03.025⟩. ⟨hal-01509487⟩



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