Glycobiology Advance Access originally published online on June 22, 2005
Glycobiology 2005 15(11):1111-1124; doi:10.1093/glycob/cwi099
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Transmembrane and secreted MUC1 probes show trafficking-dependent changes in O-glycan core profiles
2 Center of Biochemistry Medical Facility and Center for Molecular Medicine, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 Köln, Germany; 3 Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; and 4 Institute of Pathology, University of Cologne, Joseph-Stelzmann-Str. 9, 50931 Köln, Germany
1 To whom correspondence should be addressed; e-mail: franz.hanisch{at}uni-koeln.de and hughey{at}dom.pitt.edu
Received on May 3, 2005; revised on June 19, 2005; accepted on June 19, 2005
The human mucin MUC1 is expressed both as a transmembrane heterodimeric protein complex that recycles via the trans-Golgi network (TGN) and as a secreted isoform. To determine whether differences in cellular trafficking might influence the O-glycosylation profiles on these isoforms, we developed a model system consisting of membrane-bound and secretory-recombinant glycosylation probes. Secretory MUC1-S contains only a truncated repeat domain, whereas in MUC1-M constructs this domain is attached to the native transmembrane and cytoplasmic domains of MUC1 either directly (M0) or via an intermitting nonfunctional (M1) or functional sperm protein–enterokinase–agrin (SEA) module (M2); the SEA module contains a putative proteolytic cleavage site and is associated with proteins receiving extensive O-glycosylation. We showed that MUC1-M2 simulates endogenous MUC1 by recycling from the cell surface of Chinese hamster ovary (CHO) mutant ldlD14 cells through intracellular compartments where its glycosylation continues. The profiles of O-linked glycans on MUC1-S secreted by epithelial EBNA-293 and MCF-7 breast cancer cells revealed patterns dominated by core 2-based oligosaccharides. In contrast, the respective membrane-shed probes expressed in the same cells showed a complete shift to patterns dominated by sialyl core 1. In conclusion, glycan core profiles reflected the subcellular trafficking pathways of the secretory or membranous probes and the modifying activities of the resident glycosyltransferases.
Key words: mass spectrometry / MUC1 / O-glycosylation / trafficking / transmembrane protein
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  I. Breloy, T. Schwientek, B. Gries, H. Razawi, M. Macht, C. Albers, and F.-G. Hanisch Initiation of Mammalian O-Mannosylation in Vivo Is Independent of a Consensus Sequence and Controlled by Peptide Regions within and Upstream of the {alpha}-Dystroglycan Mucin Domain J. Biol. Chem., July 4, 2008; 283(27): 18832 - 18840. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Gebauer, S. Muller, F.-G. Hanisch, M. Paulsson, and R. Wagener O-Glucosylation and O-Fucosylation Occur Together in Close Proximity on the First Epidermal Growth Factor Repeat of AMACO (VWA2 Protein) J. Biol. Chem., June 27, 2008; 283(26): 17846 - 17854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J Storr, L. Royle, C. J Chapman, U. M A. Hamid, J. F Robertson, A. Murray, R. A Dwek, and P. M Rudd The O-linked glycosylation of secretory/shed MUC1 from an advanced breast cancer patient's serum Glycobiology, June 1, 2008; 18(6): 456 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wilkie, G. Picco, J. Foster, D. M. Davies, S. Julien, L. Cooper, S. Arif, S. J. Mather, J. Taylor-Papadimitriou, J. M. Burchell, et al. Retargeting of Human T Cells to Tumor-Associated MUC1: The Evolution of a Chimeric Antigen Receptor J. Immunol., April 1, 2008; 180(7): 4901 - 4909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Stork, K. A. Zettlitz, D. Muller, M. Rether, F.-G. Hanisch, and R. E. Kontermann N-Glycosylation as Novel Strategy to Improve Pharmacokinetic Properties of Bispecific Single-chain Diabodies J. Biol. Chem., March 21, 2008; 283(12): 7804 - 7812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Primo, S. Klinke, M. P. Sica, F. A. Goldbaum, J. Jakoncic, E. Poskus, and M. R. Ermacora Structure of the Mature Ectodomain of the Human Receptor-type Protein-tyrosine Phosphatase IA-2 J. Biol. Chem., February 22, 2008; 283(8): 4674 - 4681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Swanson, K. M. McDermott, P. K. Singh, J. P. Eggers, P. R. Crocker, and M. A. Hollingsworth MUC1 Is a Counter-Receptor for Myelin-Associated Glycoprotein (Siglec-4a) and Their Interaction Contributes to Adhesion in Pancreatic Cancer Perineural Invasion Cancer Res., November 1, 2007; 67(21): 10222 - 10229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kobayashi, G. Kostka, J. H. O. Garbe, D. R. Keene, H. P. Bachinger, F.-G. Hanisch, D. Markova, T. Tsuda, R. Timpl, M.-L. Chu, et al. A Comparative Analysis of the Fibulin Protein Family: BIOCHEMICAL CHARACTERIZATION, BINDING INTERACTIONS, AND TISSUE LOCALIZATION J. Biol. Chem., April 20, 2007; 282(16): 11805 - 11816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-G. Yu, N. Andrews, Q. Zhao, D. McKean, J. F. Williams, L. J. Connor, O. V. Gerasimenko, J. Hilkens, J. Hirabayashi, K. Kasai, et al. Galectin-3 Interaction with Thomsen-Friedenreich Disaccharide on Cancer-associated MUC1 Causes Increased Cancer Cell Endothelial Adhesion J. Biol. Chem., January 5, 2007; 282(1): 773 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Parry, F. G. Hanisch, S.-H. Leir, M. Sutton-Smith, H. R. Morris, A. Dell, and A. Harris N-Glycosylation of the MUC1 mucin in epithelial cells and secretions Glycobiology, July 1, 2006; 16(7): 623 - 634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Remacle, A. V. Chekanov, V. S. Golubkov, A. Y. Savinov, D. V. Rozanov, and A. Y. Strongin O-Glycosylation Regulates Autolysis of Cellular Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) J. Biol. Chem., June 23, 2006; 281(25): 16897 - 16905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Kinlough, R. J. McMahan, P. A. Poland, J. B. Bruns, K. L. Harkleroad, R. J. Stremple, O. B. Kashlan, K. M. Weixel, O. A. Weisz, and R. P. Hughey Recycling of MUC1 Is Dependent on Its Palmitoylation J. Biol. Chem., April 28, 2006; 281(17): 12112 - 12122. [Abstract] [Full Text] [PDF]
|
|