Sphingolipids Regulate the Yeast High-Osmolarity Glycerol Response Pathway

Abstract

bThe yeast high-osmolarity glycerol response (HOG) mitogen-activated protein (MAP) kinase pathway is activated in response to hyperosmotic stress via two independent osmosensing branches, the Sln1 branch and the Sho1 branch. While the mechanism by which the osmosensing machinery activates the downstream MAP kinase cascade has been well studied, the mechanism by which the machinery senses and responds to hyperosmotic stress remains to be clarified. Here we report that inhibition of the de novo sphingolipid synthesis pathway results in activation of the HOG pathway via both branches. Inhibition of ergosterol biosynthesis also induces activation of the HOG pathway. Sphingolipids and sterols are known to be tightly packed together in cell membranes to form partitioned domains called rafts. Raft-enriched detergent-resistant membranes (DRMs) contain both Sln1 and Sho1, and sphingolipid depletion and hyperosmotic stress have similar effects on the osmosensing machinery of the HOG pathway: dissociation of an Sln1-containing protein complex and elevated association of Sho1 with DRMs. These observations reveal the sphingolipid-mediated regulation of the osmosensing machinery of the HOG pathway.

Osmoregulation in Saccharomyces cerevisiae via mechanisms other than the high-osmolarity glycerol pathway

“…erg5D mutant has an osmotolerance equivalent to the WT (at 1.4 M NaCl), which is higher relative to erg2D, erg3D, erg4D or erg6D mutants. This should be seen in the light of earlier observations (Tanigawa et al, 2012) that erg2D, erg3D and erg6D mutant exhibit elevated Hog1p phosphorylation due to perturbation of the plasma membrane. However, the hyperosmotic sensitivity of these mutants observed by Kodedov a & Sychrov a, (2015) points to the essential contribution of plasma membrane functions for successful adaptation via HOG signalling.…”

Osmosensing and osmoregulation in unicellular eukaryotes

“…Earlier, Reiser et al (2003) observed that the uniform distribution on the cell membrane of Sln1 changed upon osmotic shock, forming clusters. This observation can now be explained by the experiments performed by Tanigawa et al (2012), which indicated that osmotic stress causes a partial dissociation of Sln1 from rafts. Sho1 distribution, on the other hand, was observed to remain unchanged upon osmotic shock (Reiser et al 2003); however, osmotic stress promoted the association of Sho1 to rafts (Tanigawa et al 2012), which was suggested to have an important regulatory role.…”

“…This observation can now be explained by the experiments performed by Tanigawa et al (2012), which indicated that osmotic stress causes a partial dissociation of Sln1 from rafts. Sho1 distribution, on the other hand, was observed to remain unchanged upon osmotic shock (Reiser et al 2003); however, osmotic stress promoted the association of Sho1 to rafts (Tanigawa et al 2012), which was suggested to have an important regulatory role. Further studies would undoubtedly advance our understanding of the proposed osmosensing mechanisms.…”

“…With regard to the osmosensing mechanism, an interesting recent finding has suggested that ergosterol and sphingolipids may be involved in modifying the association of Sho1 and Sln1 to membrane rafts (Tanigawa et al 2012). Membrane rafts have been suggested to play roles in cell signaling by changing local membrane structure, or by increasing the affinity or specificity of protein-protein interactions (Golub et al 2004).…”

Information processing in the adaptation of Saccharomyces cerevisiae to osmotic stress: an analysis of the phosphorelay system

“…When we performed our simulations, we assumed a linear input that turgor pressure has on the phosphorylation of Sln1, namely the linear decrease in k 1 : Although there is still ongoing research on the topic (Tanigawa et al 2012), the mechanism itself has not been characterized comprehensively. Neither has the stochastic influence of the whole ensemble of Sln1 sensing the external signal been studied.…”