Ephexin1 Is Required for Structural Maturation and Neurotransmission at the Neuromuscular Junction

SummaryThe 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.

► Ephexin1 is essential for synaptic transmission and muscle function at NMJs ► Ephexin1 is required for the topological transformation of AChR clusters ► Ephexin1 regulates the stability of AChR clusters through activation of RhoA ► Ephexin1 directs synapse maturation and maintenance in a RhoA-dependent manner