Plasma membrane stress induces relocalization of Slm proteins and activation of TORC2 to promote sphingolipid synthesis

Berchtold, D. & Walther, T. C. TORC2 plasma membrane localization is essential for cell viability and restricted to a distinct domain. Mol. Biol. Cell 20, 1565–1575 (2009).

Aronova, S. et al. Regulation of ceramide biosynthesis by TOR complex 2. Cell Metab. 7, 148–158 (2008).

Munro, S. Lipid rafts: Elusive or illusive? Cell 115, 377–388 (2003).

Ramstedt, B. & Slotte, J. P. Membrane properties of sphingomyelins. FEBS Lett. 531, 33–37 (2002).

Breslow, D. K. et al. Orm family proteins mediate sphingolipid homeostasis. Nature 463, 1048–1053 (2010).

Loewith, R. & Hall, M. N. Target of rapamycin (TOR) in nutrient signaling and growth control. Genetics 189, 1177–1201 (2011).

Lempiainen, H. et al. Sfp1 interaction with TORC1 and Mrs6 reveals feedback regulation on TOR signaling. Mol. Cell 33, 704–716 (2009).

Guan, X. L. et al. Functional interactions between sphingolipids and sterols in biological membranes regulating cell physiology. Mol. Biol. Cell 20, 2083–2095 (2009).

Dickson, R. C. Thematic review series: sphingolipids. New insights intosphingolipid metabolism and function in budding yeast. J. Lipid Res. 49, 909–921 (2008).

Urban, J. et al. Sch9 is a major target of TORC1 in Saccharomyces cerevisiae. Mol. Cell 26, 663–674 (2007).

Wanke, V. et al. Caffeine extends yeast lifespan by targeting TORC1. Mol. Microbiol. 69, 277–285 (2008).

Roelants, F. M., Baltz, A. G., Trott, A. E., Fereres, S. & Thorner, J. A protein kinase network regulates the function of aminophospholipid flippases. Proc. Natl Acad. Sci. USA 107, 34–39 (2010).

Fadri, M., Daquinag, A., Wang, S., Xue, T. & Kunz, J. The pleckstrin homology domain proteins Slm1 and Slm2 are required for actin cytoskeleton organization in yeast and bind phosphatidylinositol-4,5-bisphosphate and TORC2. Mol. Biol. Cell 16, 1883–1900 (2005).

Bultynck, G. et al. Slm1 and slm2 are novel substrates of the calcineurin phosphatase required for heat stress-induced endocytosis of the yeast uracil permease. Mol. Cell Biol. 26, 4729–4745 (2006).

Tabuchi, M., Audhya, A., Parsons, A. B., Boone, C. & Emr, S. D. The phosphatidylinositol 4,5-biphosphate and TORC2 binding proteins Slm1 and Slm2 function in sphingolipid regulation. Mol. Cell Biol. 26, 5861–5875 (2006).

Daquinag, A., Fadri, M., Jung, S. Y., Qin, J. & Kunz, J. The yeast PH domain proteins Slm1 and Slm2 are targets of sphingolipid signaling during the response to heat stress. Mol. Cell Biol. 27, 633–650 (2007).

Kamada, Y. et al. Tor2 directly phosphorylates the AGC kinase Ypk2 to regulate actin polarization. Mol. Cell Biol. 25, 7239–7248 (2005).

Gallego, O. et al. A systematic screen for protein–lipid interactions in Saccharomyces cerevisiae. Mol. Syst. Biol. 6, 430 (2010).

Walther, T. C. et al. Eisosomes mark static sites of endocytosis. Nature 439, 998–1003 (2006).

Grossmann, G. et al. Plasma membrane microdomains regulate turnover of transport proteins in yeast. J. Cell Biol. 183, 1075–1088 (2008).

Malinska, K., Malinsky, J., Opekarova, M. & Tanner, W. Visualization of protein compartmentation within the plasma membrane of living yeast cells. Mol. Biol. Cell 14, 4427–4436 (2003).

Bishop, A. C. et al. A chemical switch for inhibitor-sensitive alleles of any protein kinase. Nature 407, 395–401 (2000).

Haruki, H., Nishikawa, J. & Laemmli, U. K. The anchor-away technique: Rapid, conditional establishment of yeast mutant phenotypes. Mol. Cell 31, 925–932 (2008).

Han, S., Lone, M. A., Schneiter, R. & Chang, A. Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteins regulating lipid homeostasis and protein quality control. Proc. Natl Acad. Sci. USA 107, 5851–5856 (2010).

Roelants, F. M., Breslow, D. K., Muir, A., Weissman, J. S. & Thorner, J. Protein kinase Ypk1 phosphorylates regulatory proteins Orm1 and Orm2 to control sphingolipid homeostasis in Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 108, 19222–19227 (2011).

Frohlich, F. et al. A genome-wide screen for genes affecting eisosomes reveals Nce102 function in sphingolipid signaling. J. Cell Biol. 185, 1227–1242 (2009).

Kippenberger, S. et al. Mechanical stretch stimulates protein kinase B/Akt phosphorylation in epidermal cells via angiotensin II type 1 receptor and epidermal growth factor receptor. J. Biol. Chem. 280, 3060–3067 (2005).

Sinha, B. et al. Cells respond to mechanical stress by rapid disassembly of caveolae. Cell 144, 402–413 (2011).

Sedding, D. G. et al. Caveolin-1 facilitates mechanosensitive protein kinase B (Akt) signaling in vitro and in vivo. Circ. Res. 96, 635–642 (2005).

Yu, J. et al. Direct evidence for the role of caveolin-1 and caveolae in mechanotransduction and remodeling of blood vessels. J. Clin. Invest. 116, 1284–1291 (2006).

Zhang, B. et al. Caveolin-1 phosphorylation is required for stretch-induced EGFR and Akt activation in mesangial cells. Cell Signal 19, 1690–1700 (2007).

Janke, C. et al. A versatile toolbox for PCR-based tagging of yeast genes: New fluorescent proteins, more markers and promoter substitution cassettes. Yeast 21, 947–962 (2004).