ArticleThe Journal of biological chemistry2009
Saposin B-dependent reconstitution of arylsulfatase A activity in vitro and in cell culture models of metachromatic leukodystrophy.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Prosaposin in CNS health and disease, metabolic stress and exercise adaptation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Effective gene therapy for metachromatic leukodystrophy achieved with minimal lentiviral genomic integrations.Molecular therapy. Nucleic acids · 2025Article
- Characterization of gallbladder disease in metachromatic leukodystrophy across the lifespan.Molecular genetics and metabolism · 2025Article
- Human Saposin B Ligand Binding and Presentation to α-Galactosidase A.bioRxiv : the preprint server for biology · 2024Article
- Lysosomal processing of sulfatide analogs alters target NKT cell specificity and immune responses in cancer.The Journal of clinical investigation · 2023Article
- Animal Models for the Study of Gaucher Disease.International journal of molecular sciences · 2023Review
- Acid Sphingomyelinase, a Lysosomal and Secretory Phospholipase C, Is Key for Cellular Phospholipid Catabolism.International journal of molecular sciences · 2021Review
- Article
- The Emerging and Diverse Roles of Bis(monoacylglycero) Phosphate Lipids in Cellular Physiology and Disease.International journal of molecular sciences · 2020Review
- Leukocyte and Dried Blood Spot Arylsulfatase A Assay by Tandem Mass Spectrometry.Analytical chemistry · 2020Article
- Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches.Frontiers in medicine · 2020Review
- Membrane lipids and their degradation compounds control GM2 catabolism at intralysosomal luminal vesicles.Journal of lipid research · 2019Article
- Membrane lipids regulate ganglioside GM2 catabolism and GM2 activator protein activity.Journal of lipid research · 2015Article
- Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2.Journal of lipid research · 2014Article
- Article
- Role of endosomal membrane lipids and NPC2 in cholesterol transfer and membrane fusion.Journal of lipid research · 2010Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arylsulfatase A (ASA) catalyzes the intralysosomal desulfation of 3-O-sulfogalactosylceramide (sulfatide) to galactosylceramide. The reaction requires saposin B (Sap B), a non-enzymatic proteinaceous cofactor which presents sulfatide to the catalytic site of ASA. The lack of either ASA or Sap B results in a block of sulfatide degradation, progressive intralysosomal accumulation of sulfatide, and the fatal lysosomal storage disease metachromatic leukodystrophy. We studied the coupled Sap B-ASA reaction in vitro using detergent-free micellar and liposomal assay systems and in vivo using cell culture models of metachromatic leukodystrophy. Under in vitro conditions, the reaction had a narrow pH optimum around pH 4.3 and was inhibited by mono- and divalent cations, phosphate and sulfite. Bis(monoacylglycero) phosphate and phosphatidic acid were activators of the reaction, underscoring a significant role of acidic phosphoglycerolipids in sphingolipid degradation. Desulfation was negligible when Sap B was substituted by Sap A, C, or D. Up to a molar ratio between Sap B and sulfatide of 1:5, an elevation of Sap B concentrations caused a sharp increase of sulfatide hydrolysis, indicating the requirement of unexpected high Sap B levels for maximum turnover. Feeding of ASA-deficient, sulfatide-storing primary mouse kidney cells with ASA caused partial clearance of sulfatide. Co-feeding of Sap B or its precursor prosaposin resulted in the lysosomal uptake of the cofactor but did not promote ASA-catalyzed sulfatide hydrolysis. This suggests that Sap B is not a limiting factor of the coupled Sap B-ASA reaction in mouse kidney cells even if sulfatide has accumulated to unphysiologically high levels.
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