Distinct roles for dystroglycan, beta1 integrin and perlecan in cell surface laminin organization

M D Henry; J S Satz; C Brakebusch; M Costell; E Gustafsson; R Fässler; K P Campbell

doi:10.1242/jcs.114.6.1137

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Distinct roles for dystroglycan, beta1 integrin and perlecan in cell surface laminin organization

Journal article

Peer reviewed

Distinct roles for dystroglycan, beta1 integrin and perlecan in cell surface laminin organization

M D Henry, J S Satz, C Brakebusch, M Costell, E Gustafsson, R Fässler and K P Campbell

Journal of cell science, Vol.114(Pt 6), pp.1137-1144

03/2001

DOI: 10.1242/jcs.114.6.1137

PMID: 11228157

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Abstract

Dystroglycan (DG) is a cell surface receptor for several extracellular matrix (ECM) molecules including laminins, agrin and perlecan. Recent data indicate that DG function is required for the formation of basement membranes in early development and the organization of laminin on the cell surface. Here we show that DG-mediated laminin clustering on mouse embryonic stem (ES) cells is a dynamic process in which clusters are consolidated over time into increasingly more complex structures. Utilizing various null-mutant ES cell lines, we define roles for other molecules in this process. In beta1 integrin-deficient ES cells, laminin-1 binds to the cell surface, but fails to organize into more morphologically complex structures. This result indicates that beta1 integrin function is required after DG function in the cell surface-mediated laminin assembly process. In perlecan-deficient ES cells, the formation of complex laminin-1 structures is defective, implicating perlecan in the laminin matrix assembly process. Moreover, laminin and perlecan reciprocally modulate the organization of the other on the cell surface. Taken together, the data support a model whereby DG serves as a receptor essential for the initial binding of laminin on the cell surface, whereas beta1 integrins and perlecan are required for laminin matrix assembly processes after it binds to the cell.

Cell Line

Membrane Glycoproteins - metabolism

Cytoskeletal Proteins - genetics

Humans

Dystroglycans

Integrin beta1 - physiology

Membrane Glycoproteins - genetics

Integrin beta1 - metabolism

Membrane Glycoproteins - physiology

Animals

Heparan Sulfate Proteoglycans - genetics

Heparan Sulfate Proteoglycans - metabolism

Cytoskeletal Proteins - metabolism

Cell Membrane - metabolism

Mice

Cytoskeletal Proteins - physiology

Laminin - metabolism

Integrin beta1 - genetics

Heparan Sulfate Proteoglycans - physiology

Details

Title: Subtitle: Distinct roles for dystroglycan, beta1 integrin and perlecan in cell surface laminin organization
Creators: M D Henry - Howard Hughes Medical Institute, University of Iowa College of Medicine, Department of Physiology and Biophysics and Department of Neurology, Iowa City, IA 52242, USA
J S Satz
C Brakebusch
M Costell
E Gustafsson
R Fässler
K P Campbell
Resource Type: Journal article
Publication Details: Journal of cell science, Vol.114(Pt 6), pp.1137-1144
Publisher: England
DOI: 10.1242/jcs.114.6.1137
PMID: 11228157
ISSN: 0021-9533
eISSN: 1477-9137
Grant note: DK09712 / NIDDK NIH HHS
Language: English
Date published: 03/2001
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute; Radiation Oncology; Urology; Internal Medicine
Record Identifier: 9984068368702771

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