A novel Sit4 phosphatase complex is involved in the response to ceramide stress in yeast

Alexandra Woodacre, Museer A. Lone, Daniel Jablonowski, Roger Schneiter, Flaviano Giorgini, Raffael Schaffrath

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Ceramide is a building block for complex sphingolipids in the plasma membrane, but it also plays a significant role in secondary signalling pathways regulating cell proliferation and apoptosis in response to stress. Ceramide activated protein phosphatase activity has been previously observed in association with the Sit4 protein phosphatase. Here we find that sit4Δ mutants have decreased ceramide levels and display resistance to exogenous ceramides and phytosphingosine. Mutants lacking SIT4 or KTI12 display a shift towards nonhydroxylated forms of long chain bases and sphingolipids, suggesting regulation of hydroxylase (SUR2) or ceramide synthase by Sit4p. We have identified novel subunits of the Sit4 complex and have also shown that known Sit4 regulatory subunits-SAP proteins-are not involved in the ceramide response. This is the first observation of separation of function between Sit4 and SAP proteins. We also find that the Sit4p target Elongator is not involved in the ceramide response but that cells deficient in Kti12p-an accessory protein with an undefined regulatory role-have similar ceramide phenotypes to sit4Δ mutants. Therefore, Kti12p may play a similar secondary role in the ceramide response. This evidence points to a novel Sit4-dependent regulatory mechanism in response to ceramide stress.
    Original languageEnglish
    Number of pages7
    JournalOxidative Medicine and Cellular Longevity
    DOIs
    Publication statusPublished - 2013

    Fingerprint

    Ceramides
    Phosphoric Monoester Hydrolases
    Yeasts
    Sphingolipids
    phytosphingosine
    Phosphoprotein Phosphatases
    Protein Subunits
    Mixed Function Oxygenases
    Proteins
    Cell Proliferation
    Cell Membrane
    Observation
    Apoptosis
    Phenotype

    Cite this

    Woodacre, Alexandra ; Lone, Museer A. ; Jablonowski, Daniel ; Schneiter, Roger ; Giorgini, Flaviano ; Schaffrath, Raffael. / A novel Sit4 phosphatase complex is involved in the response to ceramide stress in yeast. In: Oxidative Medicine and Cellular Longevity. 2013.
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    abstract = "Ceramide is a building block for complex sphingolipids in the plasma membrane, but it also plays a significant role in secondary signalling pathways regulating cell proliferation and apoptosis in response to stress. Ceramide activated protein phosphatase activity has been previously observed in association with the Sit4 protein phosphatase. Here we find that sit4Δ mutants have decreased ceramide levels and display resistance to exogenous ceramides and phytosphingosine. Mutants lacking SIT4 or KTI12 display a shift towards nonhydroxylated forms of long chain bases and sphingolipids, suggesting regulation of hydroxylase (SUR2) or ceramide synthase by Sit4p. We have identified novel subunits of the Sit4 complex and have also shown that known Sit4 regulatory subunits-SAP proteins-are not involved in the ceramide response. This is the first observation of separation of function between Sit4 and SAP proteins. We also find that the Sit4p target Elongator is not involved in the ceramide response but that cells deficient in Kti12p-an accessory protein with an undefined regulatory role-have similar ceramide phenotypes to sit4Δ mutants. Therefore, Kti12p may play a similar secondary role in the ceramide response. This evidence points to a novel Sit4-dependent regulatory mechanism in response to ceramide stress.",
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    A novel Sit4 phosphatase complex is involved in the response to ceramide stress in yeast. / Woodacre, Alexandra; Lone, Museer A.; Jablonowski, Daniel; Schneiter, Roger; Giorgini, Flaviano; Schaffrath, Raffael.

    In: Oxidative Medicine and Cellular Longevity, 2013.

    Research output: Contribution to journalArticleResearchpeer-review

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    T1 - A novel Sit4 phosphatase complex is involved in the response to ceramide stress in yeast

    AU - Woodacre, Alexandra

    AU - Lone, Museer A.

    AU - Jablonowski, Daniel

    AU - Schneiter, Roger

    AU - Giorgini, Flaviano

    AU - Schaffrath, Raffael

    PY - 2013

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    N2 - Ceramide is a building block for complex sphingolipids in the plasma membrane, but it also plays a significant role in secondary signalling pathways regulating cell proliferation and apoptosis in response to stress. Ceramide activated protein phosphatase activity has been previously observed in association with the Sit4 protein phosphatase. Here we find that sit4Δ mutants have decreased ceramide levels and display resistance to exogenous ceramides and phytosphingosine. Mutants lacking SIT4 or KTI12 display a shift towards nonhydroxylated forms of long chain bases and sphingolipids, suggesting regulation of hydroxylase (SUR2) or ceramide synthase by Sit4p. We have identified novel subunits of the Sit4 complex and have also shown that known Sit4 regulatory subunits-SAP proteins-are not involved in the ceramide response. This is the first observation of separation of function between Sit4 and SAP proteins. We also find that the Sit4p target Elongator is not involved in the ceramide response but that cells deficient in Kti12p-an accessory protein with an undefined regulatory role-have similar ceramide phenotypes to sit4Δ mutants. Therefore, Kti12p may play a similar secondary role in the ceramide response. This evidence points to a novel Sit4-dependent regulatory mechanism in response to ceramide stress.

    AB - Ceramide is a building block for complex sphingolipids in the plasma membrane, but it also plays a significant role in secondary signalling pathways regulating cell proliferation and apoptosis in response to stress. Ceramide activated protein phosphatase activity has been previously observed in association with the Sit4 protein phosphatase. Here we find that sit4Δ mutants have decreased ceramide levels and display resistance to exogenous ceramides and phytosphingosine. Mutants lacking SIT4 or KTI12 display a shift towards nonhydroxylated forms of long chain bases and sphingolipids, suggesting regulation of hydroxylase (SUR2) or ceramide synthase by Sit4p. We have identified novel subunits of the Sit4 complex and have also shown that known Sit4 regulatory subunits-SAP proteins-are not involved in the ceramide response. This is the first observation of separation of function between Sit4 and SAP proteins. We also find that the Sit4p target Elongator is not involved in the ceramide response but that cells deficient in Kti12p-an accessory protein with an undefined regulatory role-have similar ceramide phenotypes to sit4Δ mutants. Therefore, Kti12p may play a similar secondary role in the ceramide response. This evidence points to a novel Sit4-dependent regulatory mechanism in response to ceramide stress.

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