Presynaptic Activity and CaMKII Modulate Retrograde Semaphorin Signaling and Synaptic Refinement
Presynaptic Activity and CaMKII Modulate Retrograde Semaphorin Signaling and Synaptic Refinement
复制标题
DOI：
10.1016/j.neuron.2010.09.005
复制
发表时间：
2010-10-07
期刊：
影响因子：
16.2
通讯作者：
Keshishian, Haig
中科院分区：
文献类型：
--
作者：
Carrillo, Robert A.;Olsen, Douglas P.;Keshishian, Haig
建立突触连接通常涉及非目标接触的活动依赖性退出。我们描述了在突触细化过程中，时间模式电活动、电压门控钙通道和CaMKII在调节果蝇运动神经元对化学排斥剂Sema-2a的反应中的体内作用。影响Sema-2a配体、丛蛋白B受体（plexB）、电压门控Ca(v)2.1钙通道（cac）或电压门控Na(v)1钠通道（mle(naP-ts)）的突变；每一种都会导致异位的神经肌肉接触。Sema-2a与这两种通道突变在基因上相互作用。cac表型通过Sema-2a突变增强，并被plexq过表达或胚胎中模式的低频（0.01 Hz）电活动抑制。异位接触的钙依赖性抑制也依赖于CaMKII的下游激活。这些结果表明，模式电活动和突触前钙信号，通过CaMKII，在突触连接细化过程中调节逆行信号的作用。
Establishing synaptic connections often involves the activity-dependent withdrawal of off-target contacts. We describe an in vivo role for temporally patterned electrical activity, voltage-gated calcium channels, and CaMKII in modulating the response of Drosophila motoneurons to the chemorepellent Sema-2a during synaptic refinement. Mutations affecting the Sema-2a ligand, the plexin B receptor (plexB), the voltage-gated Ca(v)2.1 calcium channel (cac), or the voltage-gated Na(v)1 sodium channel (mle(naP-ts);tipE) each result in ectopic neuromuscular contacts. Sema-2a interacts genetically with both of the channel mutations. The cac phenotype is enhanced by the Sema-2a mutation and is suppressed by either plexq overexpression or patterned, low-frequency (0.01 Hz) bouts of electrical activity in the embryo. The calcium-dependent suppression of ectopic contacts also depends on the downstream activation of CaMKII. These results indicate a role for patterned electrical activity and presynaptic calcium signaling, acting through CaMKII, in modulating a retrograde signal during the refinement of synaptic connections.