Back to Search
Start Over
Lysosomal Sialidase (Neuraminidase-1) Is Targeted to the Cell Surface in a Multiprotein Complex That Facilitates Elastic Fiber Assembly
- Source :
- Journal of Biological Chemistry. 281:3698-3710
- Publication Year :
- 2006
- Publisher :
- Elsevier BV, 2006.
-
Abstract
- We have established previously that the 67-kDa elastin-binding protein (EBP), identical to the spliced variant of beta-galactosidase, acts as a recyclable chaperone that facilitates secretion of tropoelastin. (Hinek, A., Keeley, F. W., and Callahan, J. W. (1995) Exp. Cell Res. 220, 312-324). We now demonstrate that EBP also forms a cell surface-targeted molecular complex with protective protein/cathepsin A and sialidase (neuraminidase-1), and provide evidence that this sialidase activity is a prerequisite for the subsequent release of tropoelastin. We found that treatment with sialidase inhibitors repressed assembly of elastic fibers in cultures of human skin fibroblasts, aortic smooth muscle cells, and ear cartilage chondrocytes and caused impaired elastogenesis in developing chick embryos. Fibroblasts derived from patients with congenital sialidosis (primary deficiency of neuraminidase-1) and galactosialidosis (secondary deficiency of neuraminidase-1) demonstrated impaired elastogenesis, which could be reversed after their transduction with neuraminidase-1 cDNA or after treatment with bacterial sialidase, which has a similar substrate specificity to human neuraminidase-1. We postulate that neuraminidase-1 catalyzes removal of the terminal sialic acids from carbohydrate chains of microfibrillar glycoproteins and other adjacent matrix glycoconjugates, unmasking their penultimate galactosugars. In turn, the exposed galactosugars interact with the galectin domain of EBP, thereby inducing the release of transported tropoelastin molecules and facilitating their subsequent assembly into elastic fibers.
- Subjects :
- DNA, Complementary
Clostridium perfringens
Galectins
Blotting, Western
Carbohydrates
Neuraminidase
Elastic fiber assembly
Cartilage metabolism
Sialidase
Models, Biological
Biochemistry
Cathepsin A
Catalysis
Chromatography, Affinity
NEU1
Chondrocytes
Tropoelastin
medicine
Humans
Sialidosis
Molecular Biology
Aorta
Cells, Cultured
Skin
biology
Cell Membrane
Muscle, Smooth
Cell Biology
Fibroblasts
beta-Galactosidase
medicine.disease
Immunohistochemistry
Protein Structure, Tertiary
Microscopy, Electron
Cartilage
Microscopy, Fluorescence
Sialic Acids
biology.protein
Electrophoresis, Polyacrylamide Gel
Lysosomes
Galactosialidosis
Protein Binding
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 281
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....b0a360963541e5898a60a9f151786466