QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online February 8, 2006
doi: 10.1242/10.1242/jcs.02780

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ruotsalainen, H. Articles by Myllylä, R. Search for Related Content PubMed PubMed Citation Articles by Ruotsalainen, H. Articles by Myllylä, R. Social Bookmarking                         What's this?

Glycosylation catalyzed by lysyl hydroxylase 3 is essential for basement membranes

Heli Ruotsalainen^1,*, Laura Sipilä^1,*, Miia Vapola¹, Raija Sormunen², Antti M. Salo¹, Lahja Uitto¹, Derry K. Mercer³, Simon P. Robins³, Maija Risteli¹, Attila Aszodi⁴, Reinhard Fässler⁴ and Raili Myllylä^1,

¹ Department of Biochemistry, Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland
² Department of Pathology, Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland
³ Rowell Research Institute, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB, UK
⁴ Department of Molecular Medicine, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany

Author for correspondence (e-mail: raili.myllyla{at}oulu.fi)

Accepted 3 November 2005

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.

Key words: Lysyl hydroxylase, Glycosylation, Basement membrane, Transgenic mouse

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				R. M. Vanacore, A.-J. L. Ham, J.-P. Cartailler, M. Sundaramoorthy, P. Todd, V. Pedchenko, Y. Sado, D.-B. Borza, and B. G. Hudson A Role for Collagen IV Cross-links in Conferring Immune Privilege to the Goodpasture Autoantigen: STRUCTURAL BASIS FOR THE CRYPTICITY OF B CELL EPITOPES J. Biol. Chem., August 15, 2008; 283(33): 22737 - 22748. [Abstract] [Full Text] [PDF]

				L. Sipila, H. Ruotsalainen, R. Sormunen, N. L. Baker, S. R. Lamande, M. Vapola, C. Wang, Y. Sado, A. Aszodi, and R. Myllyla Secretion and Assembly of Type IV and VI Collagens Depend on Glycosylation of Hydroxylysines J. Biol. Chem., November 16, 2007; 282(46): 33381 - 33388. [Abstract] [Full Text] [PDF]

				K. Takaluoma, M. Hyry, J. Lantto, R. Sormunen, R. A. Bank, K. I. Kivirikko, J. Myllyharju, and R. Soininen Tissue-specific Changes in the Hydroxylysine Content and Cross-links of Collagens and Alterations in Fibril Morphology in Lysyl Hydroxylase 1 Knock-out Mice J. Biol. Chem., March 2, 2007; 282(9): 6588 - 6596. [Abstract] [Full Text] [PDF]

				T. Holster, O. Pakkanen, R. Soininen, R. Sormunen, M. Nokelainen, K. I. Kivirikko, and J. Myllyharju Loss of Assembly of the Main Basement Membrane Collagen, Type IV, but Not Fibril-forming Collagens and Embryonic Death in Collagen Prolyl 4-Hydroxylase I Null Mice J. Biol. Chem., January 26, 2007; 282(4): 2512 - 2519. [Abstract] [Full Text] [PDF]