The RING domain of rapsyn contains E3 ligase activity. Mutation of the RING domain that abolishes the enzyme activity inhibits rapsyn- as well as agrin-induced AChR clustering in heterologous and muscle cells. Further biological and genetic studies support a working model where rapsyn a classic scaffold protein serves as an E3 ligase to induce AChR clustering and NMJ formation possibly by regulation of AChR neddylation
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