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Target-dependent retrograde signaling mediates synaptic plasticity at the Drosophila neuromuscular junction.
Developmental Neurobiology ( IF 3 ) Pub Date : 2020-02-11 , DOI: 10.1002/dneu.22731
Brett Berke 1 , Linh Le 2 , Haig Keshishian 1
Affiliation  

Neurons that innervate multiple targets often establish synapses with target‐specific strengths, and local forms of synaptic plasticity. We have examined the molecular‐genetic mechanisms that allow a single Drosophila motoneuron, the ventral Common Exciter (vCE), to establish connections with target‐specific properties at its various synaptic partners. By driving transgenes in a subset of vCE’s targets, we found that individual target cells are able to independently control the properties of vCE's innervating branch and synapses. This is achieved by means of a trans‐synaptic growth factor secreted by the target cell. At the larval neuromuscular junction, postsynaptic glutamate receptor activity stimulates the release of the BMP4/5/6 homolog Glass bottom boat (Gbb). As larvae mature and motoneuron terminals grow, Gbb activates the R‐Smad transcriptional regulator phosphorylated Mad (pMad) to facilitate presynaptic development. We found that manipulations affecting glutamate receptors or Gbb within subsets of target muscles led to local effects either specific to the manipulated muscle or by a limited gradient within the presynaptic branches. While presynaptic development depends on pMad transcriptional activity within the motoneuron nucleus, we find that the Gbb growth factor may also act locally within presynaptic terminals. Local Gbb signaling and presynaptic pMad accumulation within boutons may therefore participate in a “synaptic tagging” mechanism, to influence synaptic growth and plasticity in Drosophila.

中文翻译:

靶标依赖性逆行信号介导果蝇神经肌肉连接处的突触可塑性。

支配多个目标的神经元通常会建立具有目标特异性的突触,并形成局部形式的突触可塑性。我们已经研究了允许单个果蝇的分子遗传机制运动神经元,腹侧共同激励器(vCE),在其各种突触伙伴处建立具有靶标特异性的连接。通过在vCE的靶标子集中驱动转基因,我们发现单个靶细胞能够独立控制vCE的神经支配和突触的属性。这是通过靶细胞分泌的反突触生长因子来实现的。在幼虫神经肌肉接头处,突触后谷氨酸受体的活性刺激了BMP4 / 5/6同源玻璃底船(Gbb)的释放。随着幼虫的成熟和运动神经元末端的增长,Gbb激活R-Smad转录调节因子磷酸化的Mad(pMad),以促进突触前发育。我们发现,影响目标肌肉子集中的谷氨酸受体或Gbb的操纵会导致局部效应,该局部效应要么是受操纵的肌肉特有的,要么是突触前分支内的梯度有限。虽然突触前的发育取决于运动神经元核内的pMad转录活性,但我们发现Gbb生长因子也可能在突触前末端内局部起作用。因此,boutons中的局部Gbb信号和突触前pMad积累可能参与“突触标记”机制,从而影响突触的生长和可塑性。果蝇
更新日期:2020-02-11
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