The yeast PH domain proteins Slm1 and Slm2 are targets of sphingolipid signaling during the response to heat stress.
The PH domain-containing proteins Slm1 and Slm2 were previously identified as effectors of the phosphatidylinositol-4,5-bisphosphate (PI4,5P(2)) and TORC2 signaling pathways. Here, we demonstrate that Slm1 and Slm2 are also targets of sphingolipid signaling during the heat shock response. We show that upon depletion of cellular sphingolipid levels, Slm1 function becomes ... essential for survival under heat stress. We further demonstrate that Slm proteins are regulated by a phosphorylation/dephosphorylation cycle involving the sphingolipid-activated protein kinases Pkh1 and Pkh2 and the calcium/calmodulin-dependent protein phosphatase calcineurin. By using a combination of mass spectrometry and mutational analysis, we identified serine residue 659 in Slm1 as a site of phosphorylation. Characterization of Slm1 mutants that mimic dephosphorylated and phosphorylated states demonstrated that phosphorylation at serine 659 is vital for survival under heat stress and promotes the proper polarization of the actin cytoskeleton. Finally, we present evidence that Slm proteins are also required for the trafficking of the raft-associated arginine permease Can1 to the plasma membrane, a process that requires sphingolipid synthesis and actin polymerization. Together with previous work, our findings suggest that Slm proteins are subject to regulation by multiple signals, including PI4,5P(2), TORC2, and sphingolipids, and may thus integrate inputs from different signaling pathways to temporally and spatially control actin polarization.
Mesh Terms:
Amino Acid Transport Systems, Basic, Calcineurin, Carrier Proteins, Cell Membrane, Fatty Acids, Monounsaturated, Heat-Shock Response, Membrane Microdomains, Phosphorylation, Protein Kinases, Protein Structure, Tertiary, Protein Transport, Protein-Serine-Threonine Kinases, RNA-Binding Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Sphingolipids
Amino Acid Transport Systems, Basic, Calcineurin, Carrier Proteins, Cell Membrane, Fatty Acids, Monounsaturated, Heat-Shock Response, Membrane Microdomains, Phosphorylation, Protein Kinases, Protein Structure, Tertiary, Protein Transport, Protein-Serine-Threonine Kinases, RNA-Binding Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Sphingolipids
Mol. Cell. Biol.
Date: Jan. 01, 2007
PubMed ID: 17101780
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