title: Secretion and assembly of type IV and VI collagens depend on glycosylation of hydroxylysines.
abstract: Most lysines in type IV and VI collagens are hydroxylated and glycosylated, but the functions of these unique galactosylhydroxylysyl and glucosylgalactosylhydroxylysyl residues are poorly understood. The formation of glycosylated hydroxylysines is catalyzed by multifunctional lysyl hydroxylase 3 (LH3) in vivo, and we have used LH3-manipulated mice and cells as models to study the function of these carbohydrates. These hydroxylysine-linked carbohydrates were shown recently to be indispensable for the formation of basement membranes (Ruotsalainen, H., Sipilä, L., Vapola, M., Sormunen, R., Salo, A. M., Uitto, L., Mercer, D. K., Robins, S. P., Risteli, M., Aszodi, A., Fässler, R., and Myllylä, R. (2006) J. Cell Sci. 119, 625-635). Analysis of LH3 knock-out embryos and cells in this work indicated that loss of glycosylated hydroxylysines prevents the intracellular tetramerization of type VI collagen and leads to impaired secretion of type IV and VI collagens. Mice lacking the LH activity of LH3 produced slightly underglycosylated type IV and VI collagens with abnormal distribution. The altered distribution and aggregation of type VI collagen led to similar ultrastructural alterations in muscle to those detected in collagen VI knockout and some Ullrich congenital muscular dystrophy patients. Our results provide new information about the function of hydroxylysine-linked carbohydrates of collagens, indicating that they play an important role in the secretion, assembly, and distribution of highly glycosylated collagen types.
authors.affiliation: Department of Biocenter Oulu, University of Oulu, Oulu, FI-90014, Finland; Department of Biochemistry, University of Oulu, Oulu, FI-90014, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Sipilä
authors.affiliation: Department of Biocenter Oulu, University of Oulu, Oulu, FI-90014, Finland; Department of Biochemistry, University of Oulu, Oulu, FI-90014, Finland.
authors.forename: Heli
authors.initials: H
authors.lastname: Ruotsalainen
authors.affiliation: Department of Biocenter Oulu, University of Oulu, Oulu, FI-90014, Finland; Department of Pathology, University of Oulu, FI-90014 Oulu, Finland.
authors.forename: Raija
authors.initials: R
authors.lastname: Sormunen
authors.affiliation: Murdoch Childrens Research Institute and Department of Paediatrics, Royal Childrenŉs Hospital, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Naomi L
authors.initials: NL
authors.lastname: Baker
authors.affiliation: Murdoch Childrens Research Institute and Department of Paediatrics, Royal Childrenŉs Hospital, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Shireen R
authors.initials: SR
authors.lastname: Lamandé
authors.affiliation: Department of Biocenter Oulu, University of Oulu, Oulu, FI-90014, Finland; Department of Biochemistry, University of Oulu, Oulu, FI-90014, Finland.
authors.forename: Miia
authors.initials: M
authors.lastname: Vapola
authors.affiliation: Department of Biocenter Oulu, University of Oulu, Oulu, FI-90014, Finland; Department of Biochemistry, University of Oulu, Oulu, FI-90014, Finland.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Division of Immunology, Shigei Medical Research Institute, 2117 Yamada, Okayama 701-0202, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sado
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Attila
authors.initials: A
authors.lastname: Aszodi
authors.affiliation: Department of Biocenter Oulu, University of Oulu, Oulu, FI-90014, Finland; Department of Biochemistry, University of Oulu, Oulu, FI-90014, Finland. Electronic address: raili.myllyla@oulu.fi.
authors.forename: Raili
authors.initials: R
authors.lastname: Myllylä
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D002241:Carbohydrates / Q000737:chemistry; D003094:Collagen / Q000737:chemistry; D024141:Collagen Type IV / Q000737:chemistry*; D024142:Collagen Type VI / Q000737:chemistry*; D005347:Fibroblasts / Q000378:metabolism; D006031:Glycosylation; D006579:Heterozygote; D006901:Hydroxylysine / Q000737:chemistry*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism*; D009154:Mutation
chemical_list: D002241:Carbohydrates; D024141:Collagen Type IV; D024142:Collagen Type VI; D006901:Hydroxylysine; D003094:Collagen