Agrin Binding to 
-Dystroglycan
DOMAINS OF AGRIN NECESSARY TO INDUCE ACETYLCHOLINE RECEPTOR CLUSTERING ARE OVERLAPPING BUT NOT IDENTICAL TO THE α-DYSTROGLYCAN-BINDING REGION (*)
- From the Max-Planck-Institut für Entwicklungsbiologie, Abteilung Biochemie, D-72076 Tübingen, Federal Republic of Germany
- § To whom correspondence should be addressed. Tel.: 49-7071-601666; Fax: 49-7071-601447; :hoch{at}gen.mpibtuebingen.mpg.de.
Abstract
The synaptic basal membrane protein agrin initiates the aggregation of acetylcholine receptors at the postsynaptic membrane
of the developing neuromuscular junction. Recently, α-dystroglycan was found to be a major agrin-binding protein on the muscle
cell surface and was therefore considered a candidate agrin receptor. Employing different truncation fragments of agrin, we
determined regions of the protein involved in binding to α-dystroglycan and to heparin, an inhibitor of α-dystroglycan binding.
Deletion of a 15-kDa fragment from the C terminus of agrin had no effect on its binding to α-dystroglycan from rabbit muscle
membranes, even though this deletion completely abolishes its acetylcholine receptor aggregating activity. Conversely, deletion
of a central region does not affect agrin's clustering activity, but reduced its affinity for α-dystroglycan. Combination
of these two deletions resulted in a fragment of 
35 kDa that weakly bound to α-dystroglycan, but displayed no clustering activity. All of these fragments bound to heparin
with high affinity. Thus, α-dystroglycan does not show the binding specificity expected for an agrin receptor. Our data suggest
the existence of an additional component on the muscle cell surface that generates the observed ligand specificity.
Footnotes
-
↵* This work was supported by the Bundesministerium für Bildung, Wissenschaft, Forschung, und Technologie (Helmholtzstipendium). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- AChRs
-
acetylcholine receptors
- G-domain
-
globular domain
- EGF
-
epidermal growth factor
- DGC
-
dystrophin glycoprotein complex
- mAb
-
monoclonal antibody
- PAGE
-
polyacrylamide gel electrophoresis.
-
- Received August 16, 1995.
- Revision received December 18, 1995.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
