This Article Full Text Full Text (PDF) Supplemental material Other Versions of this Article: MCB.01204-07v1 27/24/8783    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tenno, M. Articles by Marth, J. D. Search for Related Content PubMed PubMed Citation Articles by Tenno, M. Articles by Marth, J. D.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2007, p. 8783-8796, Vol. 27, No. 24
0270-7306/07/$08.00+0     doi:10.1128/MCB.01204-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Initiation of Protein O Glycosylation by the Polypeptide GalNAcT-1 in Vascular Biology and Humoral Immunity ^,

Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California,¹ Department of Biochemistry and Biophysics, University of Rochester, School of Medicine and Dentistry, Rochester, New York,² Department of Pathology, University of California San Diego, La Jolla, California,³ Department of Anesthesiology and Critical Care Medicine, University of Muenster, Muenster, Germany,⁴ CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts,⁵ Cardiovascular Research Center and Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia,⁶ Section on Biological Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland⁷

Received 6 July 2007/ Returned for modification 18 September 2007/ Accepted 25 September 2007

Core-type protein O glycosylation is initiated by polypeptide N-acetylgalactosamine (GalNAc) transferase (ppGalNAcT) activity and produces the covalent linkage of serine and threonine residues of proteins. More than a dozen ppGalNAcTs operate within multicellular organisms, and they differ with respect to expression patterns and substrate selectivity. These distinctive features imply that each ppGalNAcT may differentially modulate regulatory processes in animal development, physiology, and perhaps disease. We found that ppGalNAcT-1 plays key roles in cell and glycoprotein selective functions that modulate the hematopoietic system. Loss of ppGalNAcT-1 activity in the mouse results in a bleeding disorder which tracks with reduced plasma levels of blood coagulation factors V, VII, VIII, IX, X, and XII. ppGalNAcT-1 further supports leukocyte trafficking and residency in normal homeostatic physiology as well as during inflammatory responses, in part by providing a scaffold for the synthesis of selectin ligands expressed by neutrophils and endothelial cells of peripheral lymph nodes. Animals lacking ppGalNAcT-1 are also markedly impaired in immunoglobulin G production, coincident with increased germinal center B-cell apoptosis and reduced levels of plasma B cells. These findings reveal that the initiation of protein O glycosylation by ppGalNAcT-1 provides a distinctive repertoire of advantageous functions that support vascular responses and humoral immunity.

Published ahead of print on 8 October 2007.

Supplemental material for this article may be found at http://mcb.asm.org/.