title: C. elegans DPY-19 is a C-mannosyltransferase glycosylating thrombospondin repeats.
abstract: Among the different types of protein glycosylation, C-mannosylation of tryptophan residues stands out because of the unique linkage formed between sugar and protein. Instead of the typical O- or N-glycosidic linkage, a C-C bond is used for attachment of a single mannose. C-mannose is characteristically found in thrombospondin type 1 repeats and in the WSXWS motif of type I cytokine receptors. The genetic base of the enzymatic activity catalyzing C-mannosylation was not known. Here we demonstrate that Caenorhabditis elegans DPY-19 is a C-mannosyltransferase. DPY-19 exhibits topological and sequential homology to the N-glycan oligosaccharyltransferase, highlighting an evolutionary link between N- and C-glycosylation. We show that the C. elegans surface receptors MIG-21 and UNC-5 are acceptor substrates of DPY-19 and that C-mannosylation is essential for the secretion of soluble MIG-21. Thereby, our data provide an explanation for the previously described identical Q neuroblast migration phenotypes of dpy-19 and mig-21 mutants.
authors.affiliation: Department of Cellular Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Falk F R
authors.initials: FF
authors.lastname: Buettner
authors.forename: Angel
authors.initials: A
authors.lastname: Ashikov
authors.forename: Birgit
authors.initials: B
authors.lastname: Tiemann
authors.forename: Ludwig
authors.initials: L
authors.lastname: Lehle
authors.forename: Hans
authors.initials: H
authors.lastname: Bakker
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006031:Glycosylation; D008358:Mannose / Q000378:metabolism; D008364:Mannosyltransferases / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D011956:Receptors, Cell Surface / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D019699:Thrombospondins / Q000737:chemistry
chemical_list: D029742:Caenorhabditis elegans Proteins; C417031:DPY-19 protein, C elegans; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D019699:Thrombospondins; C077588:UNC-5 protein, C elegans; D008364:Mannosyltransferases; D008358:Mannose