Maintenance of Acetylcholine Receptor Number by Neuregulins at the Neuromuscular Junction in Vivo

• Published in: Science (American Association for the Advancement of Science) Vol. 276; no. 5312; pp. 599 - 603
• Main Authors: Sandrock, Alfred W., Dryer, Stuart E., Rosen, Kenneth M., Gozani, Shai N., Kramer, Rainer, Theill, Lars E., Fischbach, Gerald D.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 25-04-1997; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Acetylcholine; Acetylcholine - metabolism; Acetylcholine receptors; Animals; Biological and medical sciences; Body Weight; Bungarotoxins - metabolism; DNA probes; Electrodes; Fundamental and applied biological sciences. Psychology; Glycoproteins - genetics; Glycoproteins - physiology; Heterozygote; Heterozygotes; Immunoglobulins - analysis; In Vitro Techniques; Medical research; Membrane Potentials; Mice; Motor Endplate - metabolism; Motor Endplate - physiology; Muscle fibers; Muscle Weakness - etiology; Muscles; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Nerves; Neuregulin-1; Neuregulins; Neurology; Neuromuscular junction; Neuromuscular Junction - metabolism; Neuromuscular transmission; Neurons; Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ; Protein isoforms; Receptors; Receptors, Cholinergic - genetics; Receptors, Cholinergic - metabolism; Stimuli; Synapses; Synaptic Transmission; Vertebrates: nervous system and sense organs; In vivo; Vertebrata; Cholinergic receptor; Mammalia; Mouse; Rodentia; Plasma membrane; Neurotransmitter; Density; Neuromuscular junction; Growth factor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.276.5312.599

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.