This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via ISI Web of Science (92) Citing Articles via Google Scholar Google Scholar Articles by Chui, D. Articles by Marth, J. D. Search for Related Content PubMed PubMed Citation Articles by Chui, D. Articles by Marth, J. D. Social Bookmarking                What's this?

 Previous Article  | Table of Contents |  Next Article 

Immunology
Genetic remodeling of protein glycosylation in vivo induces autoimmune disease

(autoimmunity / genetics / lupus / glomerulonephritis)

Daniel Chui^*,,, Gayathri Sellakumar^*,,, Ryan S. Green^*,, Mark Sutton-Smith^§, Tammie McQuistan, Kurt W. Marek^*,, Howard R. Morris^§, Anne Dell^§, and Jamey D. Marth^*,,¶

^* Glycobiology Research and Training Center, Howard Hughes Medical Institute,  Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093; and ^§ Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2AY, England

Edited by Stuart A. Kornfeld, Washington University School of Medicine, St. Louis, MO, and approved December 1, 2000 (received for review August 9, 2000)

Autoimmune diseases are among the most prevalent of afflictions, yet the genetic factors responsible are largely undefined. Protein glycosylation in the Golgi apparatus produces structural variation at the cell surface and contributes to immune self-recognition. Altered protein glycosylation and antibodies that recognize endogenous glycans have been associated with various autoimmune syndromes, with the possibility that such abnormalities may reflect genetic defects in glycan formation. We show that mutation of a single gene, encoding -mannosidase II, which regulates the hybrid to complex branching pattern of extracellular asparagine (N)-linked oligosaccharide chains (N-glycans), results in a systemic autoimmune disease similar to human systemic lupus erythematosus. -Mannosidase II-deficient autoimmune disease is due to an incomplete overlap of two conjoined pathways in complex-type N-glycan production. Lymphocyte development, abundance, and activation parameters are normal; however, serum immunoglobulins are increased and kidney function progressively falters as a disorder consistent with lupus nephritis develops. Autoantibody reactivity and circulating immune complexes are induced, and anti-nuclear antibodies exhibit reactivity toward histone, Sm antigen, and DNA. These findings reveal a genetic cause of autoimmune disease provoked by a defect in the pathway of protein N-glycosylation.

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

This article has been cited by other articles in HighWire Press-hosted journals:

				A. Alavi and J. S. Axford Sweet and sour: the impact of sugars on disease Rheumatology, March 27, 2008; (2008) ken081v1. [Abstract] [Full Text] [PDF]

				A. SUZUKI, R. YAMADA, and K. YAMAMOTO Citrullination by Peptidylarginine Deiminase in Rheumatoid Arthritis Ann. N.Y. Acad. Sci., June 1, 2007; 1108(1): 323 - 339. [Abstract] [Full Text] [PDF]

				J. R. Bishop and P. Gagneux Evolution of carbohydrate antigens--microbial forces shaping host glycomes? Glycobiology, May 1, 2007; 17(5): 23R - 34R. [Abstract] [Full Text] [PDF]

				S. J. Van Dyken, R. S. Green, and J. D. Marth Structural and Mechanistic Features of Protein O Glycosylation Linked to CD8+ T-Cell Apoptosis Mol. Cell. Biol., February 1, 2007; 27(3): 1096 - 1111. [Abstract] [Full Text] [PDF]

				T. Nishie, O. Miyaishi, H. Azuma, A. Kameyama, C. Naruse, N. Hashimoto, H. Yokoyama, H. Narimatsu, T. Wada, and M. Asano Development of Immunoglobulin A Nephropathy- Like Disease in {beta}-1,4-Galactosyltransferase-I-Deficient Mice Am. J. Pathol., February 1, 2007; 170(2): 447 - 456. [Abstract] [Full Text] [PDF]

				L. O. Tremblay, E. N. Kovacs, E. Daniels, N. K. Wong, M. Sutton-Smith, H. R. Morris, A. Dell, E. Marcinkiewicz, N. G. Seidah, C. McKerlie, et al. Respiratory Distress and Neonatal Lethality in Mice Lacking Golgi {alpha}1,2-Mannosidase IB Involved in N-Glycan Maturation J. Biol. Chem., January 26, 2007; 282(4): 2558 - 2566. [Abstract] [Full Text] [PDF]

				M. Hato, H. Nakagawa, M. Kurogochi, T. O. Akama, J. D. Marth, M. N. Fukuda, and S.-I. Nishimura Unusual N-Glycan Structures in {alpha}-Mannosidase II/IIx Double Null Embryos Identified by a Systematic Glycomics Approach Based on Two-dimensional LC Mapping and Matrix-dependent Selective Fragmentation Method in MALDI-TOF/TOF Mass Spectrometry Mol. Cell. Proteomics, November 1, 2006; 5(11): 2146 - 2157. [Abstract] [Full Text] [PDF]

				K. Paschinger, M. Hackl, M. Gutternigg, D. Kretschmer-Lubich, U. Stemmer, V. Jantsch, G. Lochnit, and I. B. H. Wilson A Deletion in the Golgi {alpha}-Mannosidase II Gene of Caenorhabditis elegans Results in Unexpected Non-wild-type N-Glycan Structures J. Biol. Chem., September 22, 2006; 281(38): 28265 - 28277. [Abstract] [Full Text] [PDF]

				P. K. Grewal, M. Boton, K. Ramirez, B. E. Collins, A. Saito, R. S. Green, K. Ohtsubo, D. Chui, and J. D. Marth ST6Gal-I Restrains CD22-Dependent Antigen Receptor Endocytosis and Shp-1 Recruitment in Normal and Pathogenic Immune Signaling. Mol. Cell. Biol., July 1, 2006; 26(13): 4970 - 4981. [Abstract] [Full Text] [PDF]

				A. Tramontano, T. Knight, D. Vizzuso, and S. P. Makker Nested N-Terminal Megalin Fragments Induce High-Titer Autoantibody and Attenuated Heymann Nephritis J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1979 - 1985. [Abstract] [Full Text] [PDF]

				M. Collin and V. A. Fischetti A Novel Secreted Endoglycosidase from Enterococcus faecalis with Activity on Human Immunoglobulin G and Ribonuclease B J. Biol. Chem., May 21, 2004; 279(21): 22558 - 22570. [Abstract] [Full Text] [PDF]

				A. Tramontano and S. P. Makker Conformation and Glycosylation of a Megalin Fragment Correlate with Nephritogenicity in Heymann Nephritis J. Immunol., February 15, 2004; 172(4): 2367 - 2373. [Abstract] [Full Text] [PDF]

				H. A. Doyle, R. J. Gee, and M. J. Mamula A Failure to Repair Self-Proteins Leads to T Cell Hyperproliferation and Autoantibody Production J. Immunol., September 15, 2003; 171(6): 2840 - 2847. [Abstract] [Full Text] [PDF]

				P. S. C. Leung, C. Quan, O. Park, J. Van de Water, M. J. Kurth, M. H. Nantz, A. A. Ansari, R. L. Coppel, K. S. Lam, and M. E. Gershwin Immunization with a Xenobiotic 6-Bromohexanoate Bovine Serum Albumin Conjugate Induces Antimitochondrial Antibodies J. Immunol., May 15, 2003; 170(10): 5326 - 5332. [Abstract] [Full Text] [PDF]

				K. Yasutomo Pathological lymphocyte activation by defective clearance of self-ligands in systemic lupus erythematosus Rheumatology, February 1, 2003; 42(2): 214 - 222. [Abstract] [Full Text] [PDF]

				S Lawman and M R Ehrenstein Many paths lead to lupus Lupus, December 1, 2002; 11(12): 801 - 806. [PDF]

				R. Bhattacharyya, M. Bhaumik, T. S. Raju, and P. Stanley Truncated, Inactive N-Acetylglucosaminyltransferase III (GlcNAc-TIII) Induces Neurological and Other Traits Absent in Mice That Lack GlcNAc-TIII J. Biol. Chem., July 12, 2002; 277(29): 26300 - 26309. [Abstract] [Full Text] [PDF]

				T. O. Akama, H. Nakagawa, K. Sugihara, S. Narisawa, C. Ohyama, S.-I. Nishimura, D. A. O'Brien, K. W. Moremen, J. L. Millan, and M. N. Fukuda Germ Cell Survival Through Carbohydrate-Mediated Interaction with Sertoli Cells Science, January 4, 2002; 295(5552): 124 - 127. [Abstract] [Full Text] [PDF]

				Y. Wang, J. Tan, M. Sutton-Smith, D. Ditto, M. Panico, R. M. Campbell, N. M. Varki, J. M. Long, J. Jaeken, S. R. Levinson, et al. Modeling human congenital disorder of glycosylation type IIa in the mouse: conservation of asparagine-linked glycan-dependent functions in mammalian physiology and insights into disease pathogenesis Glycobiology, December 1, 2001; 11(12): 1051 - 1070. [Abstract] [Full Text] [PDF]

				G. Landis, D. Bhole, L. Lu, and J. Tower High-Frequency Generation of Conditional Mutations Affecting Drosophila melanogaster Development and Life Span Genetics, July 1, 2001; 158(3): 1167 - 1176. [Abstract] [Full Text] [PDF]

				A. Dell and H. R. Morris Glycoprotein Structure Determination by Mass Spectrometry Science, March 23, 2001; 291(5512): 2351 - 2356. [Abstract] [Full Text]

				C. R. Bertozzi and L. L. Kiessling Chemical Glycobiology Science, March 23, 2001; 291(5512): 2357 - 2364. [Abstract] [Full Text]

Current Issue | Archives | Online Submission | Info for Authors | Editorial Board | About Subscribe | Advertise | Contact | Site Map Copyright © 2001 by the National Academy of Sciences