Reduction of Lysyl Hydroxylase 3 Causes Deleterious Changes in the Deposition and Organization of Extracellular Matrix
Maija Risteli, Heli Ruotsalainen, Antti M Salo, Raija Sormunen, Laura Sipila, Naomi L Baker, Shireen R Lamande, Leena Vimpari-Kauppinen, Raili Myllyla
JOURNAL OF BIOLOGICAL CHEMISTRY | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2009
Lysyl hydroxylase 3 (LH3) is a multifunctional enzyme possessing lysyl hydroxylase, collagen galactosyltransferase, and glucosyltransferase (GGT) activities. We report here an important role for LH3 in the organization of the extracellular matrix (ECM) and cytoskeleton. Deposition of ECM was affected in heterozygous LH3 knock-out mouse embryonic fibroblasts (MEF(+/-)) and in skin fibroblasts collected from a member of a Finnish epidermolysis bullosa simplex (EBS) family known to be deficient in GGT activity. We show the GGT deficiency to be due to a transcriptional defect in one LH3 allele. The ECM abnormalities also lead to defects in the arrangement of the cytoskeleton in both cell lines. ..View full abstract
This work was supported by grants from the Research Council for Biosciences and Environment within the Academy of Finland, the Sigrid Juselius Foundation, Biocenter Oulu, Glycoscience Graduate School, Research and Science Foundation of Farmos, Societas Scientiarum Fermica, and the Maud Kuistila Memorial Foundation.