![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 11, Issue 3, 819-831, March 2000
and
*Department of Anatomy, University of California San Francisco, San
Francisco, California 94143; and MUC1 is a mucin-like type 1 transmembrane protein associated with
the apical surface of epithelial cells. In human tumors of epithelial
origin MUC1 is overexpressed in an underglycosylated form with
truncated O-glycans and accumulates in intracellular compartments. To understand the basis for this altered subcellular localization, we compared the synthesis and trafficking of various glycosylated forms of MUC1 in normal (Chinese hamster ovary)
cells and glycosylation-defective (ldlD) cells that lack the epimerase to make UDP-Gal/GalNAc from UDP-Glc/GlcNAc. Although the MUC1 synthesized in ldlD cells was rapidly degraded, addition of GalNAc alone to the culture media resulted in stabilization and near normal
surface expression of MUC1 with truncated but sialylated O-glycans. Interestingly, the initial rate of
endocytosis of this underglycosylated MUC1 was stimulated by twofold
compared with fully glycosylated MUC1. However, the half-lives of the
two forms were not different, indicating that trafficking to lysosomes
was not affected. Both the normal and stimulated internalization of MUC1 could be blocked by hypertonic media, a hallmark of
clathrin-mediated endocytosis. MUC1 endocytosis was also blocked by
expression of a dominant-negative mutant of dynamin-1 (K44A), and MUC1
was observed in both clathrin-coated pits and vesicles by
immunoelectron microscopy of ultrathin cryosections. Our data suggest
that the subcellular redistribution of MUC1 in tumor cells could be a
direct result of altered endocytic trafficking induced by its aberrant
glycosylation; potential models are discussed. These results also
implicate a new role for O-glycans on mucin-like
membrane proteins entering the endocytic pathway through
clathrin-coated pits.
Laboratory of Epithelial
Cell Biology, Department of Medicine, Renal-Electrolyte Division,
University of Pittsburgh, Pittsburgh, Pennsylvania 15261
Corresponding author. E-mail address:
hughey{at}msx.dept-med.pitt.edu.
This article has been cited by other articles:
|
|
 |
|
  H. Setiadi and R. P. McEver Clustering endothelial E-selectin in clathrin-coated pits and lipid rafts enhances leukocyte adhesion under flow Blood, February 15, 2008; 111(4): 1989 - 1998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Mueller, O. B. Kashlan, J. B. Bruns, A. B. Maarouf, M. Aridor, T. R. Kleyman, and R. P. Hughey Epithelial Sodium Channel Exit from the Endoplasmic Reticulum Is Regulated by a Signal within the Carboxyl Cytoplasmic Domain of the {alpha} Subunit J. Biol. Chem., November 16, 2007; 282(46): 33475 - 33483. [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]
|
|
|
|
 |
|
 A. Oztan, M. Silvis, O. A. Weisz, N. A. Bradbury, S.-C. Hsu, J. R. Goldenring, C. Yeaman, and G. Apodaca Exocyst Requirement for Endocytic Traffic Directed Toward the Apical and Basolateral Poles of Polarized MDCK Cells Mol. Biol. Cell, October 1, 2007; 18(10): 3978 - 3992. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Singh, U. Samant, S. Hyland, P. R. Chaudhari, W. S. Wels, and D. Bandyopadhyay Target-specific cytotoxic activity of recombinant immunotoxin scFv(MUC1)-ETA on breast carcinoma cells and primary breast tumors Mol. Cancer Ther., February 1, 2007; 6(2): 562 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kato, C. Jeanneau, M. A. Tarp, A. Benet-Pages, B. Lorenz-Depiereux, E. P. Bennett, U. Mandel, T. M. Strom, and H. Clausen Polypeptide GalNAc-transferase T3 and Familial Tumoral Calcinosis: SECRETION OF FIBROBLAST GROWTH FACTOR 23 REQUIRES O-GLYCOSYLATION J. Biol. Chem., July 7, 2006; 281(27): 18370 - 18377. [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]
|
|
|
|
|
|
M. M. Gorska, O. Cen, Q. Liang, S. J. Stafford, and R. Alam Differential Regulation of Interleukin 5-stimulated Signaling Pathways by Dynamin J. Biol. Chem., May 19, 2006; 281(20): 14429 - 14439. [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]
|
|
|
|
|
|
K. Engelmann, C. L. Kinlough, S. Muller, H. Razawi, S. E. Baldus, R. P. Hughey, and F.-G. Hanisch Transmembrane and secreted MUC1 probes show trafficking-dependent changes in O-glycan core profiles Glycobiology, November 1, 2005; 15(11): 1111 - 1124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Kinlough, P. A. Poland, J. B. Bruns, K. L. Harkleroad, and R. P. Hughey MUC1 Membrane Trafficking Is Modulated by Multiple Interactions J. Biol. Chem., December 17, 2004; 279(51): 53071 - 53077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Ellis, M. T. Miedel, C. J. Guerriero, and O. A. Weisz ADP-ribosylation Factor 1-independent Protein Sorting and Export from the trans-Golgi Network J. Biol. Chem., December 10, 2004; 279(50): 52735 - 52743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Hughey, J. B. Bruns, C. L. Kinlough, K. L. Harkleroad, Q. Tong, M. D. Carattino, J. P. Johnson, J. D. Stockand, and T. R. Kleyman Epithelial Sodium Channels Are Activated by Furin-dependent Proteolysis J. Biol. Chem., April 30, 2004; 279(18): 18111 - 18114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. I. Wu, H. G. Munshi, R. Sen, S. J. Snipas, G. S. Salvesen, R. Fridman, and M. S. Stack Glycosylation Broadens the Substrate Profile of Membrane Type 1 Matrix Metalloproteinase J. Biol. Chem., February 27, 2004; 279(9): 8278 - 8289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Bruns, B. Hu, Y. J. Ahn, S. Sheng, R. P. Hughey, and T. R. Kleyman Multiple epithelial Na+ channel domains participate in subunit assembly Am J Physiol Renal Physiol, October 1, 2003; 285(4): F600 - F609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Hughey, G. M. Mueller, J. B. Bruns, C. L. Kinlough, P. A. Poland, K. L. Harkleroad, M. D. Carattino, and T. R. Kleyman Maturation of the Epithelial Na+ Channel Involves Proteolytic Processing of the {alpha}- and {gamma}-Subunits J. Biol. Chem., September 26, 2003; 278(39): 37073 - 37082. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Hammond, S. Carter, J. McCullough, S. Urbe, G. Vande Woude, and M. J. Clague Endosomal Dynamics of Met Determine Signaling Output Mol. Biol. Cell, April 1, 2003; 14(4): 1346 - 1354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. G. Ten Hagen, T. A. Fritz, and L. A. Tabak All in the family: the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases Glycobiology, January 1, 2003; 13(1): 1R - 16R. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. Mathoera, D. J. Kok, C. M. Verduin, and R. J. M. Nijman Pathological and Therapeutic Significance of Cellular Invasion by Proteus mirabilis in an Enterocystoplasty Infection Stone Model Infect. Immun., December 1, 2002; 70(12): 7022 - 7032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wykes, K. P. A. MacDonald, M. Tran, R. J. Quin, P. X. Xing, S. J. Gendler, D. N. J. Hart, and M. A. McGuckin MUC1 epithelial mucin (CD227) is expressed by activated dendritic cells J. Leukoc. Biol., October 1, 2002; 72(4): 692 - 701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. T. Truschel, E. Wang, W. G. Ruiz, S.-M. Leung, R. Rojas, J. Lavelle, M. Zeidel, D. Stoffer, and G. Apodaca Stretch-regulated Exocytosis/Endocytosis in Bladder Umbrella Cells Mol. Biol. Cell, March 1, 2002; 13(3): 830 - 846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Joyce-Brady, J.-C. Jean, and R. P. Hughey gamma -Glutamyltransferase and Its Isoform Mediate an Endoplasmic Reticulum Stress Response J. Biol. Chem., March 16, 2001; 276(12): 9468 - 9477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sato, M. Takahashi, Y. Shibukawa, S. K. Jain, R. Hamaoka, J.-i. Miyagawa, Y. Yaginuma, K. Honke, M. Ishikawa, and N. Taniguchi Overexpression of N-Acetylglucosaminyltransferase III Enhances the Epidermal Growth Factor-induced Phosphorylation of ERK in HeLaS3 Cells by Up-regulation of the Internalization Rate of the Receptors J. Biol. Chem., April 6, 2001; 276(15): 11956 - 11962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Bruns, M. A. Ellis, A. Jeromin, and O. A. Weisz Multiple Roles for Phosphatidylinositol 4-Kinase in Biosynthetic Transport in Polarized Madin-Darby Canine Kidney Cells J. Biol. Chem., January 11, 2002; 277(3): 2012 - 2018. [Abstract] [Full Text] [PDF]
|
|
