Dystroglycan loss disrupts polarity and β-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; John L Muschler

doi:10.1242/jcs.03103

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

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Dystroglycan loss disrupts polarity and β-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

Journal of cell science, Vol.119(19), pp.4047-4058

10/01/2006

DOI: 10.1242/jcs.03103

PMCID: PMC2996718

PMID: 16968749

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Abstract

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 β-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 β-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.

Dystroglycan

Polarity

Laminin

Integrin

Mammary

Epithelial

Details

Title: Subtitle: Dystroglycan loss disrupts polarity and β-casein induction in mammary epithelial cells by perturbing laminin anchoring
Creators: M. Lynn Weir - California Pacific Medical Center Research Institute, 475 Brannan Street, Suite 217, San Francisco, CA 94107, USA
Maria Luisa Oppizzi - California Pacific Medical Center Research Institute, 475 Brannan Street, Suite 217, San Francisco, CA 94107, USA
Michael D Henry - Howard Hughes Medical Institute, Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA 52242, USA
Akiko Onishi - California Pacific Medical Center Research Institute, 475 Brannan Street, Suite 217, San Francisco, CA 94107, USA
Kevin P Campbell - Howard Hughes Medical Institute, Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA 52242, USA
Mina J Bissell - Division of Life Sciences, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
John L Muschler - California Pacific Medical Center Research Institute, 475 Brannan Street, Suite 217, San Francisco, CA 94107, USA
Resource Type: Journal article
Publication Details: Journal of cell science, Vol.119(19), pp.4047-4058
DOI: 10.1242/jcs.03103
PMID: 16968749
PMCID: PMC2996718
NLM abbreviation: J Cell Sci
ISSN: 0021-9533
eISSN: 1477-9137
Language: English
Date published: 10/01/2006
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute; Radiation Oncology; Urology
Record Identifier: 9984020875602771

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