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PMID: 8349731 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin.

The Journal of cell biology ·Vol. 122 ·No. 4 ·1993-08-00 ·Pages 809-23

Ervasti JM, Campbell KP

Abstract

The dystrophin-glycoprotein complex was tested for interaction with several components of the extracellular matrix as well as actin. The 156-kD dystrophin-associated glycoprotein (156-kD dystroglycan) specifically bound laminin in a calcium-dependent manner and was inhibited by NaCl (IC50 = 250 mM) but was not affected by 1,000-fold (wt/wt) excesses of lactose, IKVAV, or YIGSR peptides. Laminin binding was inhibited by heparin (IC50 = 100 micrograms/ml), suggesting that one of the heparin-binding domains of laminin is involved in binding dystroglycan while negatively charged oligosaccharide moieties on dystroglycan were found to be necessary for its laminin-binding activity. No interaction between any component of the dystrophin-glycoprotein complex and fibronectin, collagen I, collagen IV, entactin, or heparan sulfate proteoglycan was detected by 125I-protein overlay and/or extracellular matrix protein-Sepharose precipitation. In addition, laminin-Sepharose quantitatively precipitated purified dystrophin-glycoprotein complex, demonstrating that the laminin-binding site is accessible when dystroglycan is associated with the complex. Dystroglycan of nonmuscle tissues also bound laminin. However, the other proteins of the striated muscle dystrophin-glycoprotein complex appear to be absent, antigenically dissimilar or less tightly associated with dystroglycan in nonmuscle tissues. Finally, we show that the dystrophin-glycoprotein complex cosediments with F-actin but does not bind calcium or calmodulin. Our results support a role for the striated muscle dystrophin-glycoprotein complex in linking the actin-based cytoskeleton with the extracellular matrix. Furthermore, our results suggest that dystrophin and dystroglycan may play substantially different functional roles in nonmuscle tissues.

MeSH Terms
Actins/physiology Amino Acid Sequence Animals Antibodies, Monoclonal Calcium/metabolism Calmodulin/metabolism Cytoskeletal Proteins/metabolism Cytoskeleton/ultrastructure Dystroglycans Dystrophin/physiology Extracellular Matrix/metabolism Glycoproteins/physiology Heparin/metabolism Laminin/physiology Macromolecular Substances Membrane Glycoproteins Molecular Sequence Data Peptides/chemistry,metabolism Protein Binding Rabbits Sarcolemma/ultrastructure
Chemicals
Actins Antibodies, Monoclonal Calmodulin Cytoskeletal Proteins Dystrophin Glycoproteins Laminin Macromolecular Substances Membrane Glycoproteins Peptides Dystroglycans Heparin Calcium
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ervasti J M
Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242.
Campbell K P
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.122.4.809
Published
1993-08-00
Pages
809-23
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2119587
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.122.4.809 PMC Full Text View journal details
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