ArticleThe Journal of biological chemistry2011
Genetic analysis of the heparan modification network in Caenorhabditis elegans.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Hedgehog pathway modulation by glypican 3-conjugated heparan sulfate.Journal of cell science · 2022Article
- Article
- Anionic and zwitterionic moieties as widespread glycan modifications in non-vertebrates.Glycoconjugate journal · 2020Review
- Heparan Sulfate Proteoglycans: Key Mediators of Stem Cell Function.Frontiers in cell and developmental biology · 2020Review
- A mutant-cell library for systematic analysis of heparan sulfate structure-function relationships.Nature methods · 2018Article
- Deciphering functional glycosaminoglycan motifs in development.Current opinion in structural biology · 2018Review
- Separation and Purification of Glycosaminoglycans (GAGs) fromBio-protocol · 2017Article
- Functional Requirements for Heparan Sulfate Biosynthesis in Morphogenesis and Nervous System Development in C. elegans.PLoS genetics · 2017Article
- Nematodes join the family of chondroitin sulfate-synthesizing organisms: Identification of an active chondroitin sulfotransferase in Caenorhabditis elegans.Scientific reports · 2016Article
- Enzyme overexpression - an exercise toward understanding regulation of heparan sulfate biosynthesis.Scientific reports · 2016Article
- SDN-1/Syndecan Acts in Parallel to the Transmembrane Molecule MIG-13 to Promote Anterior Neuroblast Migration.G3 (Bethesda, Md.) · 2015Article
- Formylglycine, a post-translationally generated residue with unique catalytic capabilities and biotechnology applications.ACS chemical biology · 2015Review
- The identification of proteoglycans and glycosaminoglycans in archaeological human bones and teeth.PloS one · 2015Article
- Syndecan promotes axon regeneration by stabilizing growth cone migration.Cell reports · 2014Article
- Combinatorial roles of heparan sulfate proteoglycans and heparan sulfates in Caenorhabditis elegans neural development.PloS one · 2014Article
- The role of syndecan-1 in cellular signaling and its effects on heparan sulfate biosynthesis in mesenchymal tumors.Frontiers in oncology · 2013Review
- Analysis of Drosophila glucuronyl C5-epimerase: implications for developmental roles of heparan sulfate sulfation compensation and 2-O-sulfated glucuronic acid.The Journal of biological chemistry · 2013Article
- The role of Drosophila heparan sulfate 6-O-endosulfatase in sulfation compensation.The Journal of biological chemistry · 2013Article
- Hitting the sweet spot.Nature methods · 2012Article
- Direct visualization of specifically modified extracellular glycans in living animals.Nature methods · 2012Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Heparan sulfates (HS) are highly modified sugar polymers in multicellular organisms that function in cell adhesion and cellular responses to protein signaling. Functionally distinct, cell type-dependent HS modification patterns arise as the result of a conserved network of enzymes that catalyze deacetylations, sulfations, and epimerizations in specific positions of the sugar residues. To understand the genetic interactions of the enzymes during the HS modification process, we have measured the composition of HS purified from mutant strains of Caenorhabditis elegans. From these measurements we have developed a genetic network model of HS modification. We find the interactions to be highly recursive positive feed-forward and negative feedback loops. Our genetic analyses show that the HS C-5 epimerase hse-5, the HS 2-O-sulfotransferase hst-2, or the HS 6-O-sulfotransferase hst-6 inhibit N-sulfation. In contrast, hse-5 stimulates both 2-O- and 6-O-sulfation and, hst-2 and hst-6 inhibit 6-O- and 2-O-sulfation, respectively. The effects of hst-2 and hst-6 on N-sulfation, 6-O-sulfation, and 2-O-sulfation appear largely dependent on hse-5 function. This core of regulatory interactions is further modulated by 6-O-endosulfatase activity (sul-1). 47% of all 6-O-sulfates get removed from HS and this editing process is dependent on hst-2, thereby providing additional negative feedback between 2-O- and 6-O-sulfation. These findings suggest that the modification patterns are highly sensitive to the relative composition of the HS modification enzymes. Our comprehensive genetic analysis forms the basis of understanding the HS modification network in metazoans.
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