spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 12 September 2006
doi: 10.1242/jcs.03103

Journal of Cell Science 119, 4047-4058 (2006)
Published by The Company of Biologists 2006
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow All Versions of this Article:
jcs.03103v1
119/19/4047    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Weir, M. L.
Right arrow Articles by Muschler, J. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Weir, M. L.
Right arrow Articles by Muschler, J. L.

Research Article

Dystroglycan loss disrupts polarity and ß-casein induction in mammary epithelial cells by perturbing laminin anchoring

M. Lynn Weir1, Maria Luisa Oppizzi1, Michael D. Henry2, Akiko Onishi1, Kevin P. Campbell2, Mina J. Bissell3 and John L. Muschler1,*

1 California Pacific Medical Center Research Institute, 475 Brannan Street, Suite 217, San Francisco, CA 94107, USA
2 Howard Hughes Medical Institute, Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA 52242, USA
3 Division of Life Sciences, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA

* Author for correspondence (e-mail: Muschler{at}cpmcri.org)

Accepted 15 June 2006

Precise contact between epithelial cells and their underlying basement membrane is crucial to the maintenance of tissue architecture and function. To understand the role that the laminin receptor dystroglycan (DG) plays in these processes, we assayed cell responses to laminin-111 following conditional ablation of DG gene (Dag1) expression in cultured mammary epithelial cells. Strikingly, DG loss disrupted laminin-111-induced polarity and ß-casein production, and abolished laminin assembly at the step of laminin binding to the cell surface. Dystroglycan re-expression restored these deficiencies. Investigations of the mechanism revealed that DG cytoplasmic sequences were not necessary for laminin assembly and signaling, and only when the entire mucin domain of extracellular DG was deleted did laminin assembly not occur. These results demonstrate that DG is essential as a laminin-111 co-receptor in mammary epithelial cells that functions by mediating laminin anchoring to the cell surface, a process that allows laminin polymerization, tissue polarity and ß-casein induction. The observed loss of laminin-111 assembly and signaling in Dag1-/- mammary epithelial cells provides insights into the signaling changes occurring in breast carcinomas and other cancers, where the binding function of DG to laminin is frequently defective.

Key words: Dystroglycan, Laminin, Polarity, Mammary, Epithelial, Integrin




This article has been cited by other articles:


Home page
 FASEB J.Home page
A. Akhavan, S. N. Crivelli, M. Singh, V. R. Lingappa, and J. L. Muschler
SEA domain proteolysis determines the functional composition of dystroglycan
FASEB J, February 1, 2008; 22(2): 612 - 621.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Fujiwara, Y. Hayashi, N. Sanzen, R. Kobayashi, C. N. Weber, T. Emoto, S. Futaki, H. Niwa, P. Murray, D. Edgar, et al.
Regulation of Mesodermal Differentiation of Mouse Embryonic Stem Cells by Basement Membranes
J. Biol. Chem., October 5, 2007; 282(40): 29701 - 29711.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. S. Yatsenko, E. E. Gray, H. R. Shcherbata, L. B. Patterson, V. D. Sood, M. M. Kucherenko, D. Baker, and H. Ruohola-Baker
A Putative Src Homology 3 Domain Binding Motif but Not the C-terminal Dystrophin WW Domain Binding Motif Is Required for Dystroglycan Function in Cellular Polarity in Drosophila
J. Biol. Chem., May 18, 2007; 282(20): 15159 - 15169.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. Xu, V. A. Spencer, and M. J. Bissell
Extracellular Matrix-regulated Gene Expression Requires Cooperation of SWI/SNF and Transcription Factors
J. Biol. Chem., May 18, 2007; 282(20): 14992 - 14999.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Harrison, S.-A. Hussain, A. C. Combs, J. M. Ervasti, P. D. Yurchenco, and E. Hohenester
Crystal Structure and Cell Surface Anchorage Sites of Laminin {alpha}1LG4-5
J. Biol. Chem., April 13, 2007; 282(15): 11573 - 11581.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2006