RT Journal Article
T1 Heterologous mammalian Akt disrupts plasma membrane homeostasis by taking over TORC2 signaling in Saccharomyces cerevisiae.
A1 Rodríguez Escudero, María Isabel
A1 Fernández-Acero Bascones, Teresa
A1 Jiménez Cid, Víctor
A1 Molina, María
AB The Akt protein kinase is the main transducer of phosphatidylinositol-3,4,5-trisphosphate (PtdIns3,4,5P) 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 PtdIns4,5P and associated to abnormal intracellular cell wall deposits. These effects of Akt were mimicked by overproduction of the PtdIns4,5P 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 PtdIns4,5P- and TORC2-signaling at the level of the Slm-Ypk complex, overriding some of its functions. Our results underscore the importance of phosphoinositide-dependent kinases as key actors in the homeostasis and dynamics of the PM.
PB Nature Research
SN 2045-2322
YR 2018
FD 2018-05-16
LK https://hdl.handle.net/20.500.14352/13362
UL https://hdl.handle.net/20.500.14352/13362
LA eng
NO Rodríguez Escudero, M. I., Fernández-Acero Bascones,, T., Jiménez Cid, V. & Molina, M. «Heterologous Mammalian Akt Disrupts Plasma Membrane Homeostasis by Taking over TORC2 Signaling in Saccharomyces Cerevisiae». Scientific Reports, vol. 8, n.o 1, mayo de 2018, p. 7732. DOI.org (Crossref), https://doi.org/10.1038/s41598-018-25717-w.
NO Ministerio de Economía, Comercio y Empresa (España)
NO Comunidad de Madrid
DS Docta Complutense
RD 17 abr 2025