ArticleThe Journal of clinical investigation2002
Hereditary sensory neuropathy type 1 mutations confer dominant negative effects on serine palmitoyltransferase, critical for sphingolipid synthesis.
Article in The Journal of clinical investigation, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 85 citations in OpenAlex.
- Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1.The Journal of clinical investigation · 2011Trial
- A Brief Review of Inherited Neuropathies: A Perspective from Saudi Arabia.Brain sciences · 2025Review
- Genetic Background of Macular Telangiectasia Type 2.International journal of molecular sciences · 2025Review
- SPTLC2 variants are associated with early-onset ALS and FTD due to aberrant sphingolipid synthesis.Annals of clinical and translational neurology · 2024Article
- Serine Palmitoyltransferase (SPT)-related Neurodegenerative and Neurodevelopmental Disorders.Journal of neuromuscular diseases · 2024Review
- Sphingolipid desaturase DEGS1 is essential for mitochondria-associated membrane integrity.The Journal of clinical investigation · 2023Article
- Plasma membrane effects of sphingolipid-synthesis inhibition by myriocin in CHO cells: a biophysical and lipidomic study.Scientific reports · 2022Article
- CHO/LY-B cell growth under limiting sphingolipid supply: Correlation between lipid composition and biophysical properties of sphingolipid-restricted cell membranes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Sphingolipids as Regulators of Neuro-Inflammation and NADPH Oxidase 2.Neuromolecular medicine · 2021Review
- Review
- A Model of Hereditary Sensory and Autonomic Neuropathy Type 1 Reveals a Role of Glycosphingolipids in Neuronal Polarity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Hereditary Sensory and Autonomic Neuropathies: Adding More to the Classification.Current neurology and neuroscience reports · 2019Review
- A perilous path: the inborn errors of sphingolipid metabolism.Journal of lipid research · 2019Review
- Comprehensive Computational Analysis of Protein Phenotype Changes Due to Plausible Deleterious Variants of Human SPTLC1 Gene.International journal of molecular and cellular medicine · 2019Article
- Quantification of 3-ketodihydrosphingosine using HPLC-ESI-MS/MS to study SPT activity in yeastJournal of lipid research · 2018Article
- Cytotoxic 1-deoxysphingolipids are metabolized by a cytochrome P450-dependent pathway.Journal of lipid research · 2017Article
- Glycosphingolipids are modulators of disease pathogenesis in amyotrophic lateral sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Human genetic disorders of sphingolipid biosynthesis.Journal of inherited metabolic disease · 2015Review
- Increased lipid droplet accumulation associated with a peripheral sensory neuropathy.Journal of chemical biology · 2014Article
- Plasma sphingolipids are biomarkers of metabolic syndrome in non-human primates maintained on a Western-style diet.International journal of obesity (2005) · 2013Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hereditary sensory neuropathy type 1 (HSN1) is a dominantly inherited degenerative disorder of the peripheral nerves. HSN1 is clinically and genetically heterogeneous. One form arises from mutations in the gene SPTLC1 encoding long-chain base 1 (LCB1), one of two subunits of serine palmitoyltransferase (SPT), the enzyme catalyzing the initial step of sphingolipid synthesis. We have examined the effects of the mutations C133Y and C133W, which we have identified in two HSN1 families, on the function of SPT. Although in HSN1 lymphoblasts, the C133Y and C133W mutations do not alter the steady-state levels of LCB1 and LCB2 subunits, they result in reduced SPT activity and sphingolipid synthesis. Moreover, in a mutant Chinese hamster ovary (CHO) cell strain with defective SPT activity due to a lack of the LCB1 subunit, these mutations impair the ability of the LCB1 subunit to complement the SPT deficiency. Furthermore, the overproduction of either the LCB1C133Y or LCB1C133W subunit inhibits SPT activity in CHO cells despite the presence of wild-type LCB1. In addition, we demonstrate that in CHO cells the mutant LCB1 proteins, similar to the normal LCB1, can interact with the wild-type LCB2 subunit. These results indicate that the HSN1-associated mutations in LCB1 confer dominant negative effects on the SPT enzyme.
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