Neurotransmitter acetylcholine negatively regulates neuromuscular synapse formation by a Cdk5-dependent mechanism

被引：176

作者：

Lin, WC ^{[1
]}

Dominguez, B ^{[1
]}

Yang, JF ^{[1
]}

Aryal, P ^{[1
]}

Brandon, EP ^{[1
]}

Gage, FH ^{[1
]}

Lee, KF ^{[1
]}

机构：

[1] Salk Inst Biol Studies, La Jolla, CA 92037 USA

来源：

NEURON | 2005年 / 46卷 / 04期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.neuron.2005.04.002

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Synapse formation requires interactions between pre- and postsynaptic cells to establish the connection of a presynaptic nerve terminal with the neurotransmitter receptor-rich postsynaptic apparatus. At developing vertebrate neuromuscular junctions, acetylcholine receptor (AChR) clusters of nascent postsynaptic apparatus are not apposed by presynaptic nerve terminals. Two opposing activities subsequently promote the formation of synapses: positive signals stabilize the innervated AChR clusters, whereas negative signals disperse those that are not innervated. Although the nerve-derived protein agrin has been suggested to be a positive signal, the negative signals remain elusive. Here, we show that cyclin-dependent kinase 5 (Cdk5) is activated by ACh agonists and is required for the ACh agonist-induced dispersion of the AChR clusters that have not been stabilized by agrin. Genetic elimination of Cdk5 or blocking ACh production prevents the dispersion of AChR clusters in agrin mutants. Therefore, we propose that ACh negatively regulates neuromuscular synapse formation through a Cdk5-dependent mechanism.

引用

页码：569 / 579

页数：11

共 70 条

[1] Rapid and reversible effects of activity on acetylcholine receptor density at the neuromuscular junction in vivo [J].