ArticlePloS one2015
Sulf1 and Sulf2 Differentially Modulate Heparan Sulfate Proteoglycan Sulfation during Postnatal Cerebellum Development: Evidence for Neuroprotective and Neurite Outgrowth Promoting Functions.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- Heparan Sulfate Proteoglycans: Master Regulators of Cellular Signaling, Tissue Development, and Neural Function.Journal of neuroscience research · 2026Review
- Secreted SULF1 protein modulates CD8 + T cell exhaustion by promoting TAM polarization in gastric cancer.Genes and immunity · 2026Article
- A non-canonical EZH2/TRIM28 epigenetic axis drives heparan sulfate remodeling and melanoma metastasis.bioRxiv : the preprint server for biology · 2026Article
- Production and inhibition of human Heparan 6-O-Endosulfatase SULF1.Glycobiology · 2025Article
- Genome-wide association study unravels mechanisms of brain glymphatic activity.Nature communications · 2025Article
- Chemistry and Function of Glycosaminoglycans in the Nervous System.Advances in neurobiology · 2023Review
- Genetic risk factors for ME/CFS identified using combinatorial analysis.Journal of translational medicine · 2022Article
- Aberrant astrocyte protein secretion contributes to altered neuronal development in multiple models of neurodevelopmental disorders.Nature neuroscience · 2022Article
- Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation.International journal of molecular sciences · 2022Review
- Proteoglycan Sulphation in the Function of the Mature Central Nervous System.Frontiers in integrative neuroscience · 2022Review
- Association between maternal depression during pregnancy and newborn DNA methylation.Translational psychiatry · 2021Article
- Differential regulation of alcohol consumption and reward by the transcriptional cofactor LMO4.Molecular psychiatry · 2021Article
- Expression of Heparan Sulfate Endosulfatases in the Adult Mouse Brain: Co-expression ofFrontiers in neuroanatomy · 2021Article
- Neural glycomics: the sweet side of nervous system functions.Cellular and molecular life sciences : CMLS · 2021Review
- Heparan Sulfate Proteoglycans Biosynthesis and Post Synthesis Mechanisms Combine Few Enzymes and Few Core Proteins to Generate Extensive Structural and Functional Diversity.Molecules (Basel, Switzerland) · 2020Review
- Deciphering the Proteome Dynamics during Development of Neurons Derived from Induced Pluripotent Stem Cells.Journal of proteome research · 2020Article
- Association between herpes simplex virus 1 exposure and the risk of depression in UK Biobank.Clinical and translational medicine · 2020Article
- B4GALNT1 induces angiogenesis, anchorage independence growth and motility, and promotes tumorigenesis in melanoma by induction of ganglioside GM2/GD2.Scientific reports · 2020Article
- Quantitative analysis of chondroitin sulfate disaccharides from human and rodent fixed brain tissue by electrospray ionization-tandem mass spectrometry.Glycobiology · 2019Article
- Enhancing the glycosciences toolkit: new GAGs in the lineup.Nature methods · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
introductionSulf1 and Sulf2 are cell surface sulfatases, which remove specific 6-O-sulfate groups from heparan sulfate (HS) proteoglycans, resulting in modulation of various HS-dependent signaling pathways. Both Sulf1 and Sulf2 knockout mice show impairments in brain development and neurite outgrowth deficits in neurons. METHODOLOGY AND MAIN
findingsTo analyze the molecular mechanisms behind these impairments we focused on the postnatal cerebellum, whose development is mainly characterized by proliferation, migration, and neurite outgrowth processes of precursor neurons. Primary cerebellar granule cells isolated from Sulf1 or Sulf2 deficient newborns are characterized by a reduction in neurite length and cell survival. Furthermore, Sulf1 deficiency leads to a reduced migration capacity. The observed impairments in cell survival and neurite outgrowth could be correlated to Sulf-specific interference with signaling pathways, as shown for FGF2, GDNF and NGF. In contrast, signaling of Shh, which determines the laminar organization of the cerebellar cortex, was not influenced in either Sulf1 or Sulf2 knockouts. Biochemical analysis of cerebellar HS demonstrated, for the first time in vivo, Sulf-specific changes of 6-O-, 2-O- and N-sulfation in the knockouts. Changes of a particular HS epitope were found on the surface of Sulf2-deficient cerebellar neurons. This epitope showed a restricted localization to the inner half of the external granular layer of the postnatal cerebellum, where precursor cells undergo final maturation to form synaptic contacts.
conclusionSulfs introduce dynamic changes in HS proteoglycan sulfation patterns of the postnatal cerebellum, thereby orchestrating fundamental mechanisms underlying brain development.
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