The Orm family proteins inhibits serine palmitoyltransferase -the enzyme that catalyzes the first step in sphingolipid synthesis. In S. cerevisiae, the two Orm proteins are thought to function redundantly in suppressing sphingolipid production. Here, we show that Orm2, in contrast, promotes production of complex sphingolipids by regulating Ypk1-dependent phosphorylation of Orm1 through control of long-chain base (LCB) levels, the initial precursors in the sphingolipid biosynthesis pathway. Using targeted lipidomic analysis of orm1Δ vs orm2Δ strains, the results showed that Orm1 regulates complex sphingolipid levels, whereas Orm2 primarily modulates the production of LCBs. We then show that reduced Orm1 phosphorylation in orm2Δ cells was mediated by LCB-dependent inactivation of AGC family protein kinase Ypk1. We further demonstrate that this Orm2-LCBs-Ypk1-Orm1 regulatory module is responsive to nitrogen availability, promoting sphingolipid synthesis under nitrogen-rich conditions. Functionally, this pathway is required for nitrogen-induced endocytosis of the general amino acid permease Gap1. Together, our findings reveal that Orm2 governs sphingolipid production and downstream endocytic events via a nitrogen-responsive LCBs-Ypk1-Orm1 signaling pathway, linking nitrogen status to sphingolipid metabolism and membrane trafficking.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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