Target recognition at the tips of postsynaptic filopodia: accumulation and function of Capricious

Target recognition at the tips of postsynaptic filopodia: accumulation and function of Capricious
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DOI:
10.1242/dev.027920
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发表时间:
2009-04-01
期刊:
影响因子:
4.6
通讯作者:
Nose, Akinao
Nose, Akinao
中科院分区:
生物学2区
文献类型:
--
作者:
Kohsaka, Hiroshi;Nose, Akinao

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虽然许多证据表明突触后动力有助于突触的形成,但很少有研究讨论它在靶点选择中可能发挥的作用。突触后运动结构是否像突触前生长锥一样寻找特定的突触伴侣细胞?本文研究了果蝇肌肉中肌足、突触后丝状足的动态变化,以及Capricious(CAPS)在突触匹配过程中的作用。CAPS是一种靶向识别分子,其胞外结构域含有富含亮氨酸的重复序列。它在胚胎/幼虫体壁肌肉的特定亚群中表达,包括肌肉12(M12)。我们提供的证据表明,暗示肌足的尖端作为初始神经肌肉识别的位点:(1)CAPS,表达为M12中的GFP融合蛋白,积累在肌足的尖端;(2)突触前运动神经元和突触后肌足的同时实时成像显示,初始神经肌肉接触发生在肌足的尖端。实时成像还显示,单个突触后肌足似乎能够区分伴侣和非伴侣突触前细胞:而许多与伴侣运动神经元的肌足接触被稳定以形成突触,与非伴侣神经元的肌足则被收回。在帽突变体,或在缺乏CAPS和密切相关的蛋白质Tartan的双突变体,我们观察到较少的接触M12的肌足和突触前生长锥的过程中,最初的神经肌肉相互作用。M12的新生突触部位也减少。这些结果为突触后丝状伪足的感觉功能提供了证据,并暗示Caps介导的识别在突触匹配的肌足尖端。
While much evidence suggests that postsynaptic dynamism contributes to the formation of synapses, few studies have addressed its possible role in target selection. Do postsynaptic motile structures seek specific synaptic partner cells, as does the presynaptic growth cone? Here we studied the dynamics of myopodia, postsynaptic filopodia in Drosophila muscles, and the role of Capricious (CAPS) during the process of synaptic matchmaking. CAPS is a target recognition molecule with an extracellular domain containing leucine-rich repeat sequences. It is expressed in specific subsets of embryonic/larval body wall muscles, including muscle 12 (M12). We provide evidence that implicates the tips of myopodia as loci of initial neuromuscular recognition: (1) CAPS, expressed as a GFP-fusion protein in M12, accumulated at the tips of myopodia; and (2) simultaneous live imaging of presynaptic motoneurons and postsynaptic myopodia revealed that initial neuromuscular contacts occur at the tips of myopodia. The live imaging also showed that individual postsynaptic myopodia appear to be able to discriminate partner and non-partner presynaptic cells: whereas many myopodial contacts with the partner motoneurons are stabilized to form synapses, those with non-partner neurons are retracted. In caps mutants, or in double mutants lacking both CAPS and the closely related protein Tartan, we observed fewer contacts between myopodia of M12 and the presynaptic growth cones during the process of initial neuromuscular interaction. The nascent synaptic sites of M12 were also reduced. These results provide evidence for the sensing function of postsynaptic filopodia, and implicate Caps-mediated recognition at the tips of myopodia in synaptic matching.