Heterologous mammalian Akt disrupts plasma membrane homeostasis by taking over TORC2 signaling in Saccharomyces cerevisiae

Scientific Reports
Isabel Rodríguez-EscuderoMaría Molina

Abstract

The Akt protein kinase is the main transducer of phosphatidylinositol-3,4,5-trisphosphate (PtdIns3,4,5P3) signaling in higher eukaryotes, controlling cell growth, motility, proliferation and survival. By co-expression of mammalian class I phosphatidylinositol 3-kinase (PI3K) and Akt in the Saccharomyces cerevisiae heterologous model, we previously described an inhibitory effect on yeast growth that relied on Akt kinase activity. Here we report that PI3K-Akt expression in yeast triggers the formation of large plasma membrane (PM) invaginations that were marked by actin patches, enriched in PtdIns4,5P2 and associated to abnormal intracellular cell wall deposits. These effects of Akt were mimicked by overproduction of the PtdIns4,5P2 effector Slm1, an adaptor of the Ypk1 and Ypk2 kinases in the TORC2 pathway. Although Slm1 was phosphorylated in vivo by Akt, TORC2-dependent Ypk1 activation did not occur. However, PI3K-activated Akt suppressed the lethality derived from inactivation of either TORC2 or Ypk protein kinases. Thus, heterologous co-expression of PI3K and Akt in yeast short-circuits PtdIns4,5P2- and TORC2-signaling at the level of the Slm-Ypk complex, overriding some of its functions. Our results underscore the importance...Continue Reading

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Citations

Jun 21, 2019·International Microbiology : the Official Journal of the Spanish Society for Microbiology·Julia María Coronas-SernaVíctor J Cid
Jul 22, 2018·Biotechnology for Biofuels·Xiao-Jing GuoYing-Jin Yuan

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Datasets Mentioned

BETA
GSE107482

Methods Mentioned

BETA
GTPases
Fluorescence microscopy
transmission electron microscopy
flow cytometry
immunoprecipitation
PCR
electrophoretic shift

Software Mentioned

Genecodis
HCImage
WinMDI
GO Term Finder

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AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.