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Molecular and Cellular Biology, July 2009, p. 3770-3782, Vol. 29, No. 13
0270-7306/09/$08.00+0     doi:10.1128/MCB.00204-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Glycosyltransferase Function in Core 2-Type Protein O Glycosylation{triangledown}

Erica L. Stone,1 Mohd Nazri Ismail,2 Seung Ho Lee,3 Ying Luu,4 Kevin Ramirez,1 Stuart M. Haslam,2 Samuel B. Ho,4 Anne Dell,2 Minoru Fukuda,3 and Jamey D. Marth1*

Howard Hughes Medical Institute and the Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093,1 Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom,2 Burnham Institute for Medical Research, La Jolla, California 92037,3 Department of Medicine, VA San Diego Healthcare System and the University of California, San Diego, La Jolla, California 921614

Received 13 February 2009/ Accepted 25 March 2009

Three glycosyltransferases have been identified in mammals that can initiate core 2 protein O glycosylation. Core 2 O-glycans are abundant among glycoproteins but, to date, few functions for these structures have been identified. To investigate the biological roles of core 2 O-glycans, we produced and characterized mice deficient in one or more of the three known glycosyltransferases that generate core 2 O-glycans (C2GnT1, C2GnT2, and C2GnT3). A role for C2GnT1 in selectin ligand formation has been described. We now report that C2GnT2 deficiency impaired the mucosal barrier and increased susceptibility to colitis. C2GnT2 deficiency also reduced immunoglobulin abundance and resulted in the loss of all core 4 O-glycan biosynthetic activity. In contrast, the absence of C2GnT3 altered behavior linked to reduced thyroxine levels in circulation. Remarkably, elimination of all three C2GnTs was permissive of viability and fertility. Core 2 O-glycan structures were reduced among tissues from individual C2GnT deficiencies and completely absent from triply deficient mice. C2GnT deficiency also induced alterations in I-branching, core 1 O-glycan formation, and O mannosylation. Although the absence of C2GnT and C4GnT activities is tolerable in vivo, core 2 O glycosylation exerts a significant influence on O-glycan biosynthesis and is important in multiple physiological processes.

* Corresponding author. Mailing address: UCSD, 9500 Gilman Drive 0625, La Jolla, CA 92093. Phone: (858) 534-6526. Fax: (858) 534-6724. E-mail: jmarth{at}me.com

{triangledown} Published ahead of print on 6 April 2009.

Molecular and Cellular Biology, July 2009, p. 3770-3782, Vol. 29, No. 13
0270-7306/09/$08.00+0     doi:10.1128/MCB.00204-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Magalhaes, A., Gomes, J., Ismail, M. N., Haslam, S. M, Mendes, N., Osorio, H., David, L., Le Pendu, J., Haas, R., Dell, A., Boren, T., Reis, C. A (2009). Fut2-null mice display an altered glycosylation profile and impaired BabA-mediated Helicobacter pylori adhesion to gastric mucosa. Glycobiology 19: 1525-1536 [Abstract] [Full Text]  


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