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.
Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR, China.
Lei
L
Shi
Busma
B
Butt
Fanny C F
FC
Ip
Ying
Y
Dai
Liwen
L
Jiang
Wing-Ho
WH
Yung
Michael E
ME
Greenberg
Amy K Y
AK
Fu
Nancy Y
NY
Ip
D000818:Animals; D002478:Cells, Cultured; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D032446:Myoblasts / Q000502:physiology / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000235:genetics / Q000254:growth & development* / Q000648:ultrastructure; D011940:Receptor Aggregation / Q000502:physiology; D011950:Receptors, Cholinergic / Q000096:biosynthesis / Q000502:physiology; D064067:Rho Guanine Nucleotide Exchange Factors; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*
D020662:Guanine Nucleotide Exchange Factors; C504481:NGEF protein, human; D011950:Receptors, Cholinergic; D064067:Rho Guanine Nucleotide Exchange Factors