ARIA, a protein that stimulates acetylcholine receptor synthesis, is a member of the neu ligand family

• Published in: Cell Vol. 72; no. 5; pp. 801 - 813
• Main Authors: Falls, Douglas L., Rosen, Kenneth M., Corfas, Gabriel, Lane, William S., Fischbach, Gerald D.
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 12.03.1993; Cell Press
• Subjects: Animals; Avian Proteins; Biological and medical sciences; Cell Line; Chick Embryo; DNA; Fundamental and applied biological sciences. Psychology; Genes; Genes. Genome; Ligands; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Motor Neurons - drug effects; Muscles - cytology; Nerve Tissue Proteins - pharmacology; Neuregulin-1; Phosphorylation - drug effects; Rats; Receptors, Cholinergic - biosynthesis; Receptors, Cholinergic - drug effects; Recombinant Proteins - pharmacology; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Tyrosine - metabolism; Vertebrata; Membrane receptor; Complementary DNA; Gene product; Protein synthesis; Gene organization; Acetylcholine; Chicken; Aves; Biological activity; Aminoacid sequence; Brain (vertebrata)
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(93)90407-H

Motor neurons stimulate their postsynaptic muscle targets to synthesize neurotransmitter receptors. Polypeptide signaling molecules may mediate this inductive interaction. Here we report the purification of ARIA, a protein that stimulates the synthesis of muscle acetylcholine receptors, and the isolation of ARIA cDNA. Recombinant ARIA increases acetylcholine receptor synthesis greater than 3-fold, and it induces tyrosine phosphorylation of a 185 kd muscle protein. The ARIA cDNA hybridizes with mRNAs that are expressed in the spinal cord from E4, a time prior to the onset of neuromuscular synapse formation, through adulthood. By E7, hybridizing mRNAs are concentrated in motor neurons. Chicken ARIA is homologous to the rat Neu differentiation factor and human heregulin, ligands for the receptor tyrosine kinase encoded by the neu (c- erbB2, HER2) proto-oncogene. Our data suggest that members of the ARIA protein family promote the formation and maintenance of chemical synapses and, furthermore, that receptor tyrosine kinases play important roles in this process.