GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:16467571

From GONUTS
Jump to: navigation, search
Citation

Ruotsalainen, H, Sipilä, L, Vapola, M, Sormunen, R, Salo, AM, Uitto, L, Mercer, DK, Robins, SP, Risteli, M, Aszodi, A, Fässler, R and Myllylä, R (2006) Glycosylation catalyzed by lysyl hydroxylase 3 is essential for basement membranes. J. Cell. Sci. 119:625-35

Abstract

Lysyl hydroxylase 3 (LH3) is a multifunctional enzyme possessing lysyl hydroxylase (LH), hydroxylysyl galactosyltransferase (GT) and galactosylhydroxylysyl glucosyltransferase (GGT) activities in vitro. To investigate the in vivo importance of LH3-catalyzed lysine hydroxylation and hydroxylysine-linked glycosylations, three different LH3-manipulated mouse lines were generated. Mice with a mutation that blocked only the LH activity of LH3 developed normally, but showed defects in the structure of the basement membrane and in collagen fibril organization in newborn skin and lung. Analysis of a hypomorphic LH3 mouse line with the same mutation, however, demonstrated that the reduction of the GGT activity of LH3 disrupts the localization of type IV collagen, and thus the formation of basement membranes during mouse embryogenesis leading to lethality at embryonic day (E) 9.5-14.5. Strikingly, survival of hypomorphic embryos and the formation of the basement membrane were directly correlated with the level of GGT activity. In addition, an LH3-knockout mouse lacked GGT activity leading to lethality at E9.5. The results confirm that LH3 has LH and GGT activities in vivo, LH3 is the main molecule responsible for GGT activity and that the GGT activity, not the LH activity of LH3, is essential for the formation of the basement membrane. Together our results demonstrate for the first time the importance of hydroxylysine-linked glycosylation for collagens.

Links

PubMed Online version:10.1242/jcs.02780

Keywords

Animals; Basement Membrane/enzymology; Catalysis; Collagen/chemistry; Collagen/metabolism; Galactosyltransferases/metabolism; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; Glucosyltransferases/metabolism; Glycosylation; Hydroxylysine/metabolism; Mice; Mice, Knockout; Mutation; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/chemistry; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/metabolism; Substrate Specificity

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:LAMA1

located_in

GO:0005604: basement membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PLOD3

acts_upstream_of_or_within

GO:0030199: collagen fibril organization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3620600
MGI:MGI:3620603

P

Seeded From UniProt

complete

MOUSE:PLOD3

acts_upstream_of_or_within

GO:0021915: neural tube development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3620600
MGI:MGI:3620601

P

Seeded From UniProt

complete

MOUSE:PLOD3

acts_upstream_of_or_within

GO:0001886: endothelial cell morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3620600
MGI:MGI:3620601

P

Seeded From UniProt

complete

MOUSE:PLOD3

acts_upstream_of_or_within

GO:0001701: in utero embryonic development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3620600
MGI:MGI:3620601

P

Seeded From UniProt

complete

MOUSE:PLOD3

acts_upstream_of_or_within

GO:0008104: protein localization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3620600
MGI:MGI:3620601

P

Seeded From UniProt

complete

MOUSE:PLOD3

enables

GO:0033823: procollagen glucosyltransferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:PLOD3

enables

GO:0008475: procollagen-lysine 5-dioxygenase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:PLOD3

acts_upstream_of_or_within

GO:0048730: epidermis morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3620603

P

Seeded From UniProt

complete

MOUSE:PLOD3

acts_upstream_of_or_within

GO:0060425: lung morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3620603

P

Seeded From UniProt

complete

MOUSE:PLOD3

acts_upstream_of_or_within

GO:0042311: vasodilation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3620600
MGI:MGI:3620601

P

Seeded From UniProt

complete

MOUSE:PLOD3

acts_upstream_of_or_within

GO:0070831: basement membrane assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3620600
MGI:MGI:3620601
MGI:MGI:3620603

P

Seeded From UniProt

complete

MOUSE:LAMA1

part_of

GO:0005604: basement membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.