Dystroglycan is a dual receptor for agrin and laminin-2 in Schwann cell membrane.
We have shown previously that alpha-dystroglycan with a molecular mass of 120 kDa is a Schwann cell receptor of laminin-2, the endoneurial isoform of laminin comprised of the alpha2, beta1, and gamma1 chains. In this paper, we show that Schwann cell alpha-dystroglycan is also a receptor of agrin, an acetylcholine receptor-aggregating molecule having partial homology to laminin alpha chains in the C terminus. Immunochemical analysis demonstrates that the peripheral nerve isoform of agrin is a 400-kDa component of the endoneurial basal lamina and is co-localized with alpha-dystroglycan surrounding the outermost layer of myelin sheath of peripheral nerve fibers. Blot overlay analysis demonstrates that both endogenous peripheral nerve agrin and laminin-2 bind to Schwann cell alpha-dystroglycan. Recombinant C-terminal fragment of the peripheral nerve isoform of agrin also binds to Schwann cell alpha-dystroglycan, confirming that the binding site for Schwann cell alpha-dystroglycan resides in the C terminus of agrin molecule. Furthermore, the binding of recombinant agrin C-terminal fragment to Schwann cell alpha-dystroglycan competes with that of laminin-2. All together, these results indicate that alpha-dystroglycan is a dual receptor for agrin and laminin-2 in the Schwann cell membrane.
Yamada
H
H
Department of Neurology and Neuroscience, Teikyo University School of Medicine, Tokyo 173, Japan.
Denzer
A J
AJ
Hori
H
H
Tanaka
T
T
Anderson
L V
LV
Fujita
S
S
Fukuta-Ohi
H
H
Shimizu
T
T
Ruegg
M A
MA
Matsumura
K
K
D018171:Agrin / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D049030:Dystroglycans; D007150:Immunohistochemistry; D007797:Laminin / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D017474:Receptors, Laminin / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism*
D018171:Agrin; D003598:Cytoskeletal Proteins; D007797:Laminin; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D017978:Receptors, Growth Factor; D017474:Receptors, Laminin; C080030:agrin receptor; D049030:Dystroglycans