Show simple item record

dc.contributor.authorHinek, A
dc.contributor.authorPshezhetsky, AV
dc.contributor.authorvon Itzstein, M
dc.contributor.authorStarcher, B
dc.date.accessioned2017-05-03T11:05:40Z
dc.date.available2017-05-03T11:05:40Z
dc.date.issued2006
dc.date.modified2009-10-19T05:22:43Z
dc.identifier.issn0021-9258
dc.identifier.doi10.1074/jbc.M508736200
dc.identifier.urihttp://hdl.handle.net/10072/13709
dc.description.abstractWe have established previously that the 67-kDa elastin-binding protein (EBP), identical to the spliced variant of ߭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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherThe American Society for Biochemistry and Molecular Biology, Inc.
dc.publisher.placeBethesda, USA
dc.publisher.urihttp://www.jbc.org/
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom3698
dc.relation.ispartofpageto3710
dc.relation.ispartofissue6
dc.relation.ispartofjournalThe Journal of Biological Chemistry
dc.relation.ispartofvolume281
dc.rights.retentionY
dc.subject.fieldofresearchChemical sciences
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchcode34
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode32
dc.titleLysosomal Sialidase (Neurominidase-1) Is Targeted to Cell Surface in the Multiprotein Complex That Facilitates Elastic Fiber Assembly
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2006
gro.hasfulltextNo Full Text
gro.griffith.authorvon Itzstein, Mark


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record