Linked Life Data

16672343

Source:http://linkedlifedata.com/resource/pubmed/id/16672343

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-5-12
pubmed:abstractText
Complex carbohydrates are highly polymorphic macromolecules that are involved in diverse biological processes; however, a detailed understanding of their function remains obscure. To better define the roles of complex carbohydrates during vertebrate embryogenesis, we have initiated an analysis of glycosyltransferase function using the zebrafish system. In this study, we report the characterization of a zebrafish beta1,4-galactosyltransferase (GalT), which has substantial homology with mammalian beta4GalT5 and is expressed zygotically throughout the zebrafish embryo. Downregulating the expression of beta4GalT5 by injection of specific morpholino oligonucleotides results in dorsalized zebrafish embryos, suggesting a role of beta4GalT5 in Bmp2-mediated specification of the dorsoventral axis. Consistent with this, morpholino-injected embryos have ventrally expanded chordin expression and reduced activation of the Bmp-dependent transcription factors Smad1/5/8. Because other growth factors, such as Egf and Fgf, require binding to extracellular proteoglycans for delivery and/or binding to their cognate receptors, we examined whether proteoglycans isolated from control and morpholino-injected embryos show differential binding affinities for Bmp2. In this regard, proteoglycans isolated from beta4GalT5 morphant embryos are underglycosylated and are unable to bind recombinant Bmp2 as efficiently as proteoglycans from control-injected embryos, whereas the binding of Bmp7 is relatively unaffected. These results suggest that beta4GalT5 is a previously unidentified zebrafish galactosyltransferase that is essential for proper patterning of the dorsoventral axis by regulating Bmp2 signaling. Furthermore, this work demonstrates that a relatively simple carbohydrate modification to endogenous proteoglycans can modulate the specificity of cytokine signaling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
133
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2233-41
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16672343-Amino Acid Sequence, pubmed-meshheading:16672343-Animals, pubmed-meshheading:16672343-Animals, Genetically Modified, pubmed-meshheading:16672343-Body Patterning, pubmed-meshheading:16672343-Bone Morphogenetic Protein 2, pubmed-meshheading:16672343-Bone Morphogenetic Proteins, pubmed-meshheading:16672343-Cloning, Molecular, pubmed-meshheading:16672343-Embryo, Nonmammalian, pubmed-meshheading:16672343-Galactosyltransferases, pubmed-meshheading:16672343-Gene Expression Regulation, Developmental, pubmed-meshheading:16672343-Glycoproteins, pubmed-meshheading:16672343-Glycosylation, pubmed-meshheading:16672343-Humans, pubmed-meshheading:16672343-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:16672343-Molecular Sequence Data, pubmed-meshheading:16672343-Molecular Weight, pubmed-meshheading:16672343-Phenotype, pubmed-meshheading:16672343-Phylogeny, pubmed-meshheading:16672343-Protein Binding, pubmed-meshheading:16672343-Proteoglycans, pubmed-meshheading:16672343-Sequence Alignment, pubmed-meshheading:16672343-Sequence Homology, Amino Acid, pubmed-meshheading:16672343-Smad Proteins, pubmed-meshheading:16672343-Transforming Growth Factor beta, pubmed-meshheading:16672343-Zebrafish
pubmed:year
2006
pubmed:articleTitle
A beta1,4-galactosyltransferase is required for Bmp2-dependent patterning of the dorsoventral axis during zebrafish embryogenesis.
pubmed:affiliation
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural