BMP signaling and microtubule organization regulate synaptic strength.

BMP signaling and microtubule organization regulate synaptic strength.
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DOI:
10.1016/j.neuroscience.2015.01.069
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发表时间:
2015-04-16
期刊:
影响因子:
3.3
通讯作者:
Isacoff, E. Y.
Isacoff, E. Y.
中科院分区:
医学3区
文献类型:
--
作者:
Ball, R. W.;Peled, E. S.;Guerrero, G.;Isacoff, E. Y.

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一个神经元和多个突触后伙伴之间的突触传递的强度可以有相当大的变化。我们已经研究了突触异质性使用的mammatergic果蝇神经肌肉接头(NMJ),其中包含多个不同强度的运动轴突和肌纤维之间的突触连接。在幼虫NMJ中,存在从弱近端到强远端终扣的突触传递梯度。我们用突触后靶向荧光钙传感器SynapCam对突触传递进行成像,以研究决定突触强度的分子通路并建立此梯度。我们发现骨形态发生蛋白(BMP)信号通路的突变破坏了强远端终扣的产生。我们发现,强连接包含未捆绑的微管在终扣,这表明微管组织的作用,在传输强度。痉挛素突变,破坏微管,破坏了传输梯度,支持这一解释。我们建议,BMP通路,以前显示的功能在突触生长的稳态调节,也促进突触传递的空间选择性的方式,取决于微管系统。
The strength of synaptic transmission between a neuron and multiple postsynaptic partners can vary considerably. We have studied synaptic heterogeneity using the glutamatergic Drosophila neuromuscular junction (NMJ), which contains multiple synaptic connections of varying strength between a motor axon and muscle fiber. In larval NMJs, there is a gradient of synaptic transmission from weak proximal to strong distal boutons. We imaged synaptic transmission with the postsynaptically targeted fluorescent calcium sensor SynapCam, to investigate the molecular pathways that determine synaptic strength and set up this gradient. We discovered that mutations in the Bone Morphogenetic Protein (BMP) signaling pathway disrupt production of strong distal boutons. We find that strong connections contain unbundled microtubules in the boutons, suggesting a role for microtubule organization in transmission strength. The spastin mutation, which disorganizes microtubules, disrupted the transmission gradient, supporting this interpretation. We propose that the BMP pathway, shown previously to function in the homeostatic regulation of synaptic growth, also boosts synaptic transmission in a spatially selective manner that depends on the microtubule system.
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