Ephexin1 is required for structural maturation and neurotransmission at the neuromuscular junction.

The maturation of neuromuscular junctions (NMJs) requires the topological transformation of postsynaptic acetylcholine receptor (AChR)-containing structures from a simple plaque to an elaborate structure composed of pretzel-like branches. This maturation process results in the precise apposition of the presynaptic and postsynaptic specializations. However, little is known about the molecular mechanisms underlying the plaque-to-pretzel transition of AChR clusters. In this study, we identify an essential role for the RhoGEF ephexin1 in the maturation of AChR clusters. Adult ephexin1(-/-) mice exhibit severe muscle weakness and impaired synaptic transmission at the NMJ. Intriguingly, when ephexin1 expression is deficient in vivo, the NMJ fails to mature into the pretzel-like shape, and such abnormalities can be rescued by re-expression of ephexin1. We further demonstrate that ephexin1 regulates the stability of AChR clusters in a RhoA-dependent manner. Taken together, our findings reveal an indispensible role for ephexin1 in regulating the structural maturation and neurotransmission of NMJs. Copyright 2010 Elsevier Inc. All rights reserved.

Citation

Lei Shi, Busma Butt, Fanny C F Ip, Ying Dai, Liwen Jiang, Wing-Ho Yung, Michael E Greenberg, Amy K Y Fu, Nancy Y Ip. Ephexin1 is required for structural maturation and neurotransmission at the neuromuscular junction. Neuron. 2010 Jan 28;65(2):204-16

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PMID: 20152127

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