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

Article Abstract:

The purification and cDNA cloning of ARIA, a 42-kd protein which stimulates the synthesis of muscle acetylcholine receptors (AChR), is reported. The protein encoded by ARIA cDNA promoted the tyrosine phosphorylation of a 185-kilodalton muscle protein and increased AChR synthesis more than 3-fold. The protein was shown to be homologous to the Neu differentiation factor and to human heregulin, which have been identified as ligands for the 185-kilodalton receptor tyrosine kinase. These results indicate a role for ARIA and ARIA-activated tyrosine kinases in the differentiation of the neuromuscular junction and possibly of interneuronal synapses.

Identification and classification, Peptide regulatory factors

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Synaptic structure and development: the neuromuscular junction

Article Abstract:

Most of the present knowledge on synaptogenesis derives from studies on the neuromuscular junction, which is the only synapse in vertebrates and invertebrates whose structure and function are sufficiently well understood to permit developmental analysis. The cytological and molecular architecture of this synapse is described, as well as the complex series of inductive interactions between nerve and muscle that regulates synaptic development. Some of the soluble signaling molecules involved in these interactions are described, and the regulatory circuits that define synaptic maturation are presented.

Neural transmission, Synaptic transmission

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Defective neuromuscular synaptogenesis in agrin-deficient mutant mice

Article Abstract:

Agrin activates rapsyn to initiate AChR clustering and modulates integrin-dependent transcriptional regulation. Agrin-deficient mice exhibit impaired pre- and postsynaptic differentiation with aberrant acetylcholine receptor (AChR) aggregates. This abnormality is caused by the lack of nerve-derived z-agrin and muscle agrin. The presence of uninnervated AChR clusters and synaptic nuclei with impaired synaptic functions were also detected. The presence of AChR aggregates suggests that other nerve-associated organizing signals trigger postsynaptic differentiation.

Physiological aspects, Nerves, Growth, Motor neurons, Cell differentiation, Acetylcholine, Acetylcholine receptors

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