Acetylcholine receptor inducing activity (ARIA) is a glycoprotein released from the motor neuron to stimulate the synthesis of acetylcholine receptors (AChRs) on the muscle fiber at vertebrate neuromuscular junction. Transcript encoding ARIA was detected not only in brain but also in muscle, and immunohistochemical staining showed that the muscle-derived ARIA was restricted to the neuromuscular junctions. RT-PCR analysis revealed three biological active isoforms of ARIA mRNA in chick muscle, namely ARIAβ1, ARIAα2 and ARIAβ2. The expression of these ARIA isoforms in muscle changed during development, denervation and nerve regeneration. A splicing variation in the region between the Ig-like and the EGF-like domains of ARIA was also revealed; without amino acid insertion (ARIAsp0), a 17- a...[ Read more ]

Acetylcholine receptor inducing activity (ARIA) is a glycoprotein released from the motor neuron to stimulate the synthesis of acetylcholine receptors (AChRs) on the muscle fiber at vertebrate neuromuscular junction. Transcript encoding ARIA was detected not only in brain but also in muscle, and immunohistochemical staining showed that the muscle-derived ARIA was restricted to the neuromuscular junctions. RT-PCR analysis revealed three biological active isoforms of ARIA mRNA in chick muscle, namely ARIAβ1, ARIAα2 and ARIAβ2. The expression of these ARIA isoforms in muscle changed during development, denervation and nerve regeneration. A splicing variation in the region between the Ig-like and the EGF-like domains of ARIA was also revealed; without amino acid insertion (ARIAsp0), a 17- amino acid insertion (ARIAsp17), or a 34-amino acid insertion (ARIAsp34) was identified. The expression of ARIAsp0, ARIAsp17 and ARIAsp34 in chick muscle remained unchanged during development and after nerve injury. The specific expression of these ARIA isoforms in cultured myotubes was not affected by drug treatments or by co-culturing with neurons. In addition, site-directed mutagenesis revealed that the release of the active EGF-like domain was at the carboxyl-terminus of the spacer domain. The proteolytic site within H137-F148 might be essential for the release of the EGF-like domain at the neuromuscular junction.