Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-4-7
pubmed:abstractText
Heparan sulfate proteoglycans (HSPGs) participate in a wide range of biological processes through interactions with a number of ligand proteins. The nature of these interactions largely depends on the heparan sulfate (HS) moiety of HSPGs, which undergoes a series of modifications by various HS-modifying enzymes (HSMEs). Although the effects of alterations in a single HSME on physiological processes have started to be studied, it remains elusive how a combination of these molecules control the structure and function of HS. Here we systematically manipulated the HS structures and analyzed their effect on morphogenesis and signaling, using the genetically tractable model organism, Drosophila. We generated transgenic fly strains overexpressing HSMEs alone or in combination. Unsaturated disaccharide analyses of HS showed that expression of various HSMEs generates distinct HS structures, and the enzymatic activities of HSMEs are influenced by coexpression of other HSMEs. Furthermore, these transgenic HSME animals showed a different extent of lethality, and a subset of HSMEs caused specific morphological defects due to defective activities of Wnt and bone morphogenetic protein signaling. There is no obvious relationship between HS unsaturated disaccharide composition and developmental defects in HSME animals, suggesting that other structural factors, such as domain organization or sulfation sequence, might regulate the function of HS.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Carbohydrate Epimerases, http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Heparan Sulfate Proteoglycans, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Sulfotransferases, http://linkedlifedata.com/resource/pubmed/chemical/Wnt1 Protein, http://linkedlifedata.com/resource/pubmed/chemical/dpp protein, Drosophila, http://linkedlifedata.com/resource/pubmed/chemical/heparan sulfate 6-O-sulfotransferase, http://linkedlifedata.com/resource/pubmed/chemical/heparan-sulfate 2-sulfotransferase, http://linkedlifedata.com/resource/pubmed/chemical/sfl protein, Drosophila, http://linkedlifedata.com/resource/pubmed/chemical/wg protein, Drosophila
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1460-2423
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
607-18
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
In vivo manipulation of heparan sulfate structure and its effect on Drosophila development.
pubmed:affiliation
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, 55455, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural