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, Françoise M, Chauhan, Neha, Muir, Alexander, Davis, Jameson C, Menon, Anant K, Levine, Timothy P, and Thorner, Jeremy
- Subjects
Biotechnology ,Genetics ,1.1 Normal biological development and functioning ,Underpinning research ,Generic health relevance ,Cell Membrane ,Endoplasmic Reticulum ,Homeostasis ,Mechanistic Target of Rapamycin Complex 2 ,Phosphorylation ,Protein Domains ,Protein Serine-Threonine Kinases ,Saccharomyces cerevisiae ,Saccharomyces cerevisiae Proteins ,Sphingolipids ,Sterols ,Stress ,Physiological ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - 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