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REGULATION OF PLASMA MEMBRANE‐LOCALIZED STRESS RESPONSE SIGNALING BY INOSITOL‐CONTAINING SPHINGOLIPIDS
Author(s) -
Jesch Stephen A.,
Gaspar Maria L.,
Henry Susan A.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.816.1
Subject(s) - sphingolipid , inositol , microbiology and biotechnology , signal transduction , biology , regulator , gq alpha subunit , kinase , lipid signaling , biochemistry , chemistry , receptor , g protein , gene
Inositol‐containing sphingolipids at the plasma membrane play important roles in regulating stress response pathways, which are critical for lipid homeostasis and cell viability. In the present study, we show that that inositol starvation of budding yeast results in a dramatic reorganization of composition of inositol‐containing sphingolipids, most notably a 50% reduction in the level of mannosyl‐inositolphosphorylceramide (MIPC). To identify lipid‐mediated signaling networks that respond the reprogramming of inositol‐sphingolipid levels, we carried out gene expression profiling following inositol starvation. These results revealed that genes controlled by three stress response pathways, including protein kinase C, HOG signaling and calcineurin pathways, are highly up‐regulated following inositol starvation. Consistent with these findings, slt2 Δ, hog1 Δ, and cnb1 Δ mutants exhibit inositol auxotrophy. Moreover, cells lacking Csg2p, a Ca 2+ ‐binding regulator of MIPC synthesis, constitutively activate protein kinase C, HOG pathway, and calcineurin signaling, suggesting a critical role for MIPC in stress response signaling. However, regulation of the ER‐localized unfolded protein response was unaffected. Together, these results suggest a feedback mechanism for regulating sphingolipid‐mediated signaling by coordinated regulation of stress response pathways.