The fully linked HTML version of this article has now been published.
JCS ePress
online publication date 12 Sep 2006
doi: 10.1242/jcs.03103
Research Article
Dystroglycan loss disrupts polarity and 
-casein induction in mammary epithelial cells by perturbing laminin anchoring
M. Lynn Weir,
Maria Luisa Oppizzi,
Michael D. Henry,
Akiko Onishi,
Kevin P. Campbell,
Mina J. Bissell,
and
John L. Muschler*
* Author for correspondence (e-mail: Muschler{at}cpmcri.org)
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 
-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 -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.
This article has been cited by other articles:
|
|
|
|
 
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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
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
