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Science 25 April 1997:
Vol. 276. no. 5312, pp. 599 - 603
DOI: 10.1126/science.276.5312.599
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Maintenance of Acetylcholine Receptor Number by Neuregulins at the Neuromuscular Junction in Vivo

Alfred W. Sandrock Jr., * Stuart E. Dryer, *dagger Kenneth M. Rosen, Shai N. Gozani, Rainer Kramer, Lars E. Theill, Gerald D. Fischbach ddagger

ARIA (for acetylcholine receptor-inducing activity), a protein purified on the basis of its ability to stimulate acetylcholine receptor (AChR) synthesis in cultured myotubes, is a member of the neuregulin family and is present at motor endplates. This suggests an important role for neuregulins in mediating the nerve-dependent accumulation of AChRs in the postsynaptic membrane. Nerve-muscle synapses have now been analyzed in neuregulin-deficient animals. Mice that are heterozygous for the deletion of neuregulin isoforms containing an immunoglobulin-like domain are myasthenic. Postsynaptic AChR density is significantly reduced, as judged by the decrease in the mean amplitude of spontaneous miniature endplate potentials and bungarotoxin binding. On the other hand, the mean amplitude of evoked endplate potentials was not decreased, due to an increase in the number of quanta released per impulse, a compensation that has been observed in other myasthenic states. Thus, the density of AChRs in the postsynaptic membrane depends on immunoglobulin-containing neuregulin isoforms throughout the life of the animal.

A. W. Sandrock Jr., Department of Neurobiology, Harvard Medical School, Boston, MA 02115, and Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
S. E. Dryer, K. M. Rosen, S. N. Gozani, G. D. Fischbach, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
R. Kramer and L. E. Theill, Amgen, Thousand Oaks, CA 91320, USA.
*   These authors contributed equally to this work.

dagger    Present address: Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA.

ddagger    To whom correspondence should be addressed.

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