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© The Rockefeller University Press, 0021-9525/2001//1441 $5.00
The Journal of Cell Biology, Volume 153, Number 7, , 2001 1441-1452

Effects of Purified Recombinant Neural and Muscle Agrin on Skeletal Muscle Fibers in Vivo

^a Department of Physiology, University of Oslo, 0317 Oslo, Norway
^b Department of Anatomy, University of Oslo, 0317 Oslo, Norway
^c C.N.R. Center for Cellular and Molecular Pharmacology, Department of Medical Pharmacology, University of Milano, 20129 Milan, Italy
Department of Pharmacology/Neurobiology, Biozentrum, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.41-61-267-220841-61-267-2214

gabriela.bezakova{at}unibas.ch

Aggregation of acetylcholine receptors (AChRs) in muscle fibers by nerve-derived agrin plays a key role in the formation of neuromuscular junctions. So far, the effects of agrin on muscle fibers have been studied in culture systems, transgenic animals, and in animals injected with agrin–cDNA constructs. We have applied purified recombinant chick neural and muscle agrin to rat soleus muscle in vivo and obtained the following results. Both neural and muscle agrin bind uniformly to the surface of innervated and denervated muscle fibers along their entire length. Neural agrin causes a dose-dependent appearance of AChR aggregates, which persist 7 wk after a single application. Muscle agrin does not cluster AChRs and at 10 times the concentration of neural agrin does not reduce binding or AChR-aggregating activity of neural agrin. Electrical muscle activity affects the stability of agrin binding and the number, size, and spatial distribution of the neural agrin–induced AChR aggregates. Injected agrin is recovered from the muscles together with laminin and both proteins coimmunoprecipitate, indicating that agrin binds to laminin in vivo. Thus, the present approach provides a novel, simple, and efficient method for studying the effects of agrin on muscle under controlled conditions in vivo.

Key Words: agrin • acetylcholine receptors • laminin • electrical activity • neuromuscular junction

© 2001 The Rockefeller University Press

Abbreviations used in this paper: AChR, acetylcholine receptor; EB, extraction buffer; Fl-BuTx, FITC-bungarotoxin; NMJ, neuromuscular junction; PFA, paraformaldehyde; Rh-BuTx, TRITC--bungarotoxin; SOL, soleus.

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