Ezrin-dependent regulation of the actin cytoskeleton by beta-dystroglycan.
Dystroglycan is part of an adhesion receptor complex linking the extracellular matrix to the actin cytoskeleton. Previous studies have implicated dystroglycan in basement membrane formation and as a crucial link between dystrophin and laminin in muscle. We report here a further novel function for dystroglycan which appears to be in addition to its role as an adhesion molecule. beta-dystroglycan has been localized to microvilli structures in a number of cell types where it associates with the cytoskeletal adaptor ezrin, through which it is able to modulate the actin cytoskeleton and induce peripheral filopodia and microvilli. Ezrin is able to interact with dystroglycan through a cluster of basic residues in the juxtamembrane region of dystroglycan, and mutation of these residues both prevents ezrin binding and the induction of actin-rich surface protrusions. These studies reveal novel functions and additional signalling roles for dystroglycan, raising the possibility of new avenues for therapeutic intervention in diseases such as Duchenne muscular dystrophy.
Spence
H J
HJ
CRUK Beatson Laboratories, Garscube Estate, Glasgow, UK.
Chen
Y-J
YJ
Batchelor
C L
CL
Higginson
J R
JR
Suila
H
H
Carpen
O
O
Winder
S J
SJ
D000199:Actins / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics / Q000502:physiology; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism*; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D000099149:Ezrin
D000199:Actins; D003598:Cytoskeletal Proteins; D049030:Dystroglycans; D010750:Phosphoproteins; D000099149:Ezrin; C483081:DAG1 protein, human