Glycobiology, Vol 8, 67-75, Copyright © 1998 by Society for Glycobiology
BJ van Klinken, AW Einerhand, HA Buller and J Dekker
Mucins are synthesized and secreted by many epithelia. They are complex
glycoproteins that offer cytoprotection. In their functional configuration,
mucins form oligomers by a biosynthetic process that is poorly understood.
A family of four human gastrointestinal mucin genes (MUC2, MUC5AC, MUC5B,
and MUC6) is clustered to chromosome 11p15.5. To study oligomerization of
these related mucins, we performed metabolic labeling experiments with
[35S]amino acids in LS174T cells, and isolated mucin precursors by specific
immunoprecipitations that were analyzed on SDS-PAGE. Each of the precursors
of MUC2, MUC5AC, MUC5B, and MUC6 formed a single species of
disulfide-linked homo-oligomer within 1 h after pulse labeling. Based on
apparent molecular masses, these oligomeric precursors were most likely
dimers. Inhibition of vesicular RER-to-Golgi transport, with brefeldin A
and CCCP, did not affect the dimerization of MUC2 precursors, localizing
dimerization to the RER. O-Glycosylation of MUC2 followed dimerization.
Inhibition of N- glycosylation by tunicamycin retarded, but did not
inhibit, dimerization, indicating that N-glycans play a role in efficient
dimerization of MUC2 precursors. Based on sequence homology, the ability of
MUC2, MUC5AC, MUC5B and MUC6 to dimerize most likely resides in their
C-terminal domains. Thus, the RER-localized dimerization of secretory
mucins likely proceeds by similar mechanisms, which is an essential step in
the formation of the human gastrointestinal mucus- gels.
ORIGINAL ARTICLES
The oligomerization of a family of four genetically clustered human gastrointestinal mucins
Pediatric Gastroenterology and Nutrition, Academic Medical Center, Rm 68-260, University of Amsterdam, Amsterdam, The Netherlands.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Finzi, V. Barbu, P.-R. Burgel, M. Mergey, K. S. Kirkwood, E. C. Wick, J.-Y. Scoazec, F. Peschaud, F. Paye, J. A. Nadel, et al. MUC5AC, a Gel-Forming Mucin Accumulating in Gallstone Disease, Is Overproduced via an Epidermal Growth Factor Receptor Pathway in the Human Gallbladder Am. J. Pathol., December 1, 2006; 169(6): 2031 - 2041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. E. Vinall, J. C. Fowler, A. L. Jones, H. J. Kirkbride, C. de Bolós, A. Laine, N. Porchet, J. R. Gum, Y. S. Kim, F. M. Moss, et al. Polymorphism of Human Mucin Genes in Chest Disease . Possible Significance of MUC2 Am. J. Respir. Cell Mol. Biol., November 1, 2000; 23(5): 678 - 686. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Perez-Vilar and R. L. Hill The Structure and Assembly of Secreted Mucins J. Biol. Chem., November 5, 1999; 274(45): 31751 - 31754. [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Winterford, M. D. Walsh, B. A. Leggett, and J. R. Jass Ultrastructural Localization of Epithelial Mucin Core Proteins in Colorectal Tissues J. Histochem. Cytochem., August 1, 1999; 47(8): 1063 - 1074. [Abstract] [Full Text]
|
|
|
|
|
|
A. Herrmann, J. R. Davies, G. Lindell, S. Martensson, N. H. Packer, D. M. Swallow, and I. Carlstedt Studies on the "Insoluble" Glycoprotein Complex from Human Colon. IDENTIFICATION OF REDUCTION-INSENSITIVE MUC2 OLIGOMERS AND C-TERMINAL CLEAVAGE J. Biol. Chem., May 28, 1999; 274(22): 15828 - 15836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Perez-Vilar and R. L. Hill Identification of the Half-cystine Residues in Porcine Submaxillary Mucin Critical for Multimerization through the D-domains. ROLES OF THE CGLCG MOTIF IN THE D1- AND D3-DOMAINS J. Biol. Chem., December 18, 1998; 273(51): 34527 - 34534. [Abstract] [Full Text] [PDF]
|
|