Processing of ARIA and release from isolated nerve terminals

The neuromuscular junction is a specialized synapse in that every action po tential in the presynaptic nerve terminal results in an action potential in the postsynaptic membrane, unlike most interneuronal synapses where a sing le presynaptic input makes only a small contribution to the population post synaptic response. The postsynaptic membrane at the neuromuscular junction contains a high density of neurotransmitter (acetylcholine) receptors and a high density of voltage-gated Na+ channels. Thus, the large acetylcholine activated current occurs at the same site where the threshold for action po tential generation is low. Acetylcholine receptor inducing activity (ARIA), a 42 kD protein, that stimulates synthesis of acetylcholine receptors and voltage-gated Na+ channels in cultured myotubes, probably plays the same ro les at developing and mature motor endplates in vivo. ARIA is synthesized a s part of a larger, transmembrane, precursor protein called proARIA. Delive ry of ARIA from motor neuron cell bodies in the spinal cord to the target e ndplates involves several steps, including proteolytic cleavage of proARIA. ARIA is also expressed in the central nervous system and it is abundant in the molecular layer of the cerebellum. In this paper we describe our first experiments on the processing and release of ARIA from subcellular fractio ns containing synaptosomes from the chick cerebellum as a model system.