Serotonin-Induced Regulation of the Actin Network for Learning-Related Synaptic Growth Requires Cdc42, N-WASP, and PAK in Aplysia Sensory Neurons
Serotonin-Induced Regulation of the Actin Network for Learning-Related Synaptic Growth Requires Cdc42, N-WASP, and PAK in Aplysia Sensory Neurons
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DOI：
10.1016/j.neuron.2005.01.044
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发表时间：
2005-03
期刊：
影响因子：
16.2
通讯作者：
H. Udo;I. Jin;Joung-Hun Kim;Hsiu-Ling Li;Trisha Y Youn;R. Hawkins;E. Kandel;C. H. Bailey
中科院分区：
文献类型：
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作者：
H. Udo;I. Jin;Joung-Hun Kim;Hsiu-Ling Li;Trisha Y Youn;R. Hawkins;E. Kandel;C. H. Bailey
应用艰难梭菌毒素B（一种Rho家族的GTP酶抑制剂）于运动神经元突触的感觉神经元阻滞长期易化和由5-羟色胺（5-HT）重复脉冲诱导的新感觉神经元静脉曲张的相关生长。我们已经分离出编码ApCdc 42、Rho、Rac和Cdc 42的cDNAs，发现Rho和Rac没有影响，但在感觉神经元中过表达ApCdc 42的显性负突变体或其下游效应物PAK和N-WASP的CRIB结构域选择性地减少突触强度和结构的长期变化。FRET分析表明，5-HT激活ApCdc 42在一个子集的静脉曲张接触突触后运动神经元，这种激活是依赖于PI 3 K和PLC信号通路。5-HT诱导的ApCdc 42激活启动突触前肌动蛋白网络的重组，导致丝状伪足的生长，其中一些是学习相关的新的感觉神经元静脉曲张形成的形态学前体。
Application ofClostridium difficiletoxin B, an inhibitor of the Rho family of GTPases, at theAplysiasensory to motor neuron synapse blocks long-term facilitation and the associated growth of new sensory neuron varicosities induced by repeated pulses of serotonin (5-HT). We have isolated cDNAs encodingAplysia Rho,Rac, andCdc42and found that Rho and Rac had no effect but that overexpression in sensory neurons of a dominant-negative mutant of ApCdc42 or the CRIB domains of its downstream effectors PAK and N-WASP selectively reduces the long-term changes in synaptic strength and structure. FRET analysis indicates that 5-HT activates ApCdc42 in a subset of varicosities contacting the postsynaptic motor neuron and that this activation is dependent on the PI3K and PLC signaling pathways. The 5-HT-induced activation of ApCdc42 initiates reorganization of the presynaptic actin network leading to the outgrowth of filopodia, some of which are morphological precursors for the learning-related formation of new sensory neuron varicosities.