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Original Article |
Correspondence to: Gabriela Bezakova, Department of Pharmacology/Neurobiology, Biozentrum, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland. Tel:41-61-267-2214 Fax:41-61-267-2208 E-mail:gabriela.bezakova{at}unibas.ch.
In innervated skeletal muscle fibers, dystrophin and ß-dystroglycan form rib-like structures (costameres) that appear as predominantly transverse stripes over Z and M lines. Here, we show that the orientation of these stripes becomes longitudinal in denervated muscles and transverse again in denervated electrically stimulated muscles. Skeletal muscle fibers express nonneural (muscle) agrin whose function is not well understood. In this work, a single application of 
10 nM purified recombinant muscle agrin into denervated muscles preserved the transverse orientation of costameric proteins that is typical for innervated muscles, as did a single application of 1 µM neural agrin. At lower concentration, neural agrin induced acetylcholine receptor aggregates, which colocalized with longitudinally oriented ß-dystroglycan, dystrophin, utrophin, syntrophin, rapsyn, and ß2-laminin in denervated unstimulated fibers and with the same but transversely oriented proteins in innervated or denervated stimulated fibers. The results indicate that costameres are plastic structures whose organization depends on electrical muscle activity and/or muscle agrin.
Key Words: agrin, acetylcholine receptor, cytoskeleton, electrical activity, costameres
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