Noncanonical regulation of phosphatidylserine metabolism by a Sec14-like protein and a lipid kinase
| Autor: | Yaxi Wang, Aby Grabon, Vytas A. Bankaitis, Sin Man Lam, Peihua Yuan, Michal Eisenberg-Bord, Maya Schuldiner, Zehua Wang, Ashutosh Tripathi, Martin A. Rodriguez, Max Lönnfors, Dongju Lee |
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| Rok vydání: | 2019 |
| Předmět: |
Phosphatidylethanolamine
Saccharomyces cerevisiae Proteins Kinase Endoplasmic reticulum Phosphatidylethanolamines Phosphatase Membrane Proteins Biological Transport Cell Biology Phosphatidylserine Phosphatidylserines Saccharomyces cerevisiae Biology Lipid Metabolism Membrane contact site Article Cell biology Cell Metabolism chemistry.chemical_compound Metabolism chemistry Phosphatidylinositol Phospholipid Transfer Proteins 1-Phosphatidylinositol 4-Kinase Phosphatidylinositol transfer protein |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 |
| Popis: | Yeast Psd2-catalyzed decarboxylation of phosphatidylserine to phosphatidylethanolamine is activated in a noncanonical mechanism by the Sec14-like phosphatidylinositol-transfer protein Sfh4 via a specific protein–protein interaction, and by Stt4 PtdIns 4-OH kinase–mediated control of phosphatidylserine accessibility to the enzyme. The yeast phosphatidylserine (PtdSer) decarboxylase Psd2 is proposed to engage in a membrane contact site (MCS) for PtdSer decarboxylation to phosphatidylethanolamine (PtdEtn). This proposed MCS harbors Psd2, the Sec14-like phosphatidylinositol transfer protein (PITP) Sfh4, the Stt4 phosphatidylinositol (PtdIns) 4-OH kinase, the Scs2 tether, and an uncharacterized protein. We report that, of these components, only Sfh4 and Stt4 regulate Psd2 activity in vivo. They do so via distinct mechanisms. Sfh4 operates via a mechanism for which its PtdIns-transfer activity is dispensable but requires an Sfh4-Psd2 physical interaction. The other requires Stt4-mediated production of PtdIns-4-phosphate (PtdIns4P), where Stt4 (along with the Sac1 PtdIns4P phosphatase and endoplasmic reticulum–plasma membrane tethers) indirectly modulate Psd2 activity via a PtdIns4P homeostatic mechanism that influences PtdSer accessibility to Psd2. These results identify an example in which the biological function of a Sec14-like PITP is cleanly uncoupled from its canonical in vitro PtdIns-transfer activity and challenge popular functional assumptions regarding lipid-transfer protein involvements in MCS function. |
| Databáze: | OpenAIRE |
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