1. TOR complex 2-regulated protein kinase Ypk1 controls sterol distribution by inhibiting StARkin domain-containing proteins located at plasma membrane-endoplasmic reticulum contact sites.
- Author
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Roelants FM, Chauhan N, Muir A, Davis JC, Menon AK, Levine TP, and Thorner J
- Subjects
- Homeostasis, Phosphorylation, Protein Domains, Sphingolipids metabolism, Stress, Physiological, Cell Membrane metabolism, Endoplasmic Reticulum metabolism, Mechanistic Target of Rapamycin Complex 2 metabolism, Protein Serine-Threonine Kinases chemistry, Protein Serine-Threonine Kinases metabolism, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins chemistry, Saccharomyces cerevisiae Proteins metabolism, Sterols metabolism
- Abstract
In our proteome-wide screen, Ysp2 (also known as Lam2/Ltc4) was identified as a likely physiologically relevant target of the TOR complex 2 (TORC2)-dependent protein kinase Ypk1 in the yeast Saccharomyces cerevisiae. Ysp2 was subsequently shown to be one of a new family of sterol-binding proteins located at plasma membrane (PM)-endoplasmic reticulum (ER) contact sites. Here we document that Ysp2 and its paralogue Lam4/Ltc3 are authentic Ypk1 substrates in vivo and show using genetic and biochemical criteria that Ypk1-mediated phosphorylation inhibits the ability of these proteins to promote retrograde transport of sterols from the PM to the ER. Furthermore, we provide evidence that a change in PM sterol homeostasis promotes cell survival under membrane-perturbing conditions known to activate TORC2-Ypk1 signaling. These observations define the underlying molecular basis of a new regulatory mechanism for cellular response to plasma membrane stress.
- Published
- 2018
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