ArticleProceedings of the National Academy of Sciences of the United States of America2015
Elevation of 20-carbon long chain bases due to a mutation in serine palmitoyltransferase small subunit b results in neurodegeneration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 79 citations in OpenAlex.
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- Sphingolipids in human disease: organ-specific pathologies, chain-length-dependent effects, and translational implications.Journal of translational medicine · 2026Review
- SPTSSA facilitates gastric cancer progression with modulating PD-L1 in immunomicroenvironment through Wnt/β-catenin pathway.Cellular oncology (Dordrecht, Netherlands) · 2025Article
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- Human genetic defects of sphingolipid synthesis.Journal of inherited metabolic disease · 2025Review
- Atypical sphingosine-1-phosphate metabolites-biological implications of alkyl chain length.Pflugers Archiv : European journal of physiology · 2024Review
- Recurrent de novoJournal of neurology, neurosurgery, and psychiatry · 2024Article
- Serine Palmitoyltransferase (SPT)-related Neurodegenerative and Neurodevelopmental Disorders.Journal of neuromuscular diseases · 2024Review
- Lipidomics profiling reveals distinct patterns of plasma sphingolipid alterations in Alzheimer's disease and vascular dementia.Alzheimer's research & therapy · 2023Article
- Comprehensive analysis for the immune related biomarkers of platinum-based chemotherapy in ovarian cancer.Translational oncology · 2023Article
- SPTSSA variants alter sphingolipid synthesis and cause a complex hereditary spastic paraplegia.Brain : a journal of neurology · 2023Article
- Neuronal Ganglioside and Glycosphingolipid (GSL) Metabolism and Disease : Cascades of Secondary Metabolic Errors Can Generate Complex Pathologies (in LSDs).Advances in neurobiology · 2023Article
- Sphingolipids in neurodegenerative diseases.Frontiers in neuroscience · 2023Review
- Reduced urine volume and changed renal sphingolipid metabolism in P2ry14-deficient mice.Frontiers in cell and developmental biology · 2023Article
- Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology.Frontiers in physiology · 2023Review
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Authors and funding
13 authors at 4 institutions in 1 country.
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Abstract
Sphingolipids typically have an 18-carbon (C18) sphingoid long chain base (LCB) backbone. Although sphingolipids with LCBs of other chain lengths have been identified, the functional significance of these low-abundance sphingolipids is unknown. The LCB chain length is determined by serine palmitoyltransferase (SPT) isoenzymes, which are trimeric proteins composed of two large subunits (SPTLC1 and SPTLC2 or SPTLC3) and a small subunit (SPTssa or SPTssb). Here we report the identification of an Sptssb mutation, Stellar (Stl), which increased the SPT affinity toward the C18 fatty acyl-CoA substrate by twofold and significantly elevated 20-carbon (C20) LCB production in the mutant mouse brain and eye, resulting in surprising neurodegenerative effects including aberrant membrane structures, accumulation of ubiquitinated proteins on membranes, and axon degeneration. Our work demonstrates that SPT small subunits play a major role in controlling SPT activity and substrate affinity, and in specifying sphingolipid LCB chain length in vivo. Moreover, our studies also suggest that excessive C20 LCBs or C20 LCB-containing sphingolipids impair protein homeostasis and neural functions.
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