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.
Shi
Lei
L
Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR, China.
Butt
Busma
B
Ip
Fanny C F
FC
Dai
Ying
Y
Jiang
Liwen
L
Yung
Wing-Ho
WH
Greenberg
Michael E
ME
Fu
Amy K Y
AK
Ip
Nancy Y
NY
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