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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Molecular determinants of synapsin targeting to presynaptic terminals.
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Molecular determinants of synapsin targeting to presynaptic terminals.

机译：突触前突触终端的分子决定因素。

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摘要

Although synapsins are abundant synaptic vesicle proteins that are widely used as markers of presynaptic terminals, the mechanisms that target synapsins to presynaptic terminals have not been elucidated. We have addressed this question by imaging the targeting of green fluorescent protein-tagged synapsins in cultured hippocampal neurons. Whereas all synapsin isoforms targeted robustly to presynaptic terminals in wild-type neurons, synapsin Ib scarcely targeted in neurons in which all synapsins were knocked-out. Coexpression of other synapsin isoforms significantly strengthened the targeting of synapsin Ib in knock-out neurons, indicating that heterodimerization is required for synapsin Ib to target. Truncation mutagenesis revealed that synapsin Ia targets via distributed binding sites that include domains B, C, and E. Although domain A was not necessary for targeting, its presence enhanced targeting. Domain D inhibited targeting, but this inhibition was overcome by domain E. Thus, multiple intermolecular and intramolecular interactions are required for synapsins to target to presynaptic terminals.
机译：尽管突触蛋白是丰富的突触小泡蛋白，被广泛用作突触前末端的标记，但尚未阐明将突触素靶向突触前末端的机制。我们通过对培养的海马神经元中绿色荧光蛋白标记的突触素进行靶向成像，解决了这个问题。尽管所有突触蛋白同工型都强烈靶向野生型神经元中的突触前末端，但突触蛋白Ib几乎不靶向其中所有突触蛋白都被敲除的神经元。其他突触蛋白同工型的共表达显着增强了敲除神经元中突触蛋白Ib的靶向性，表明突触蛋白Ib靶向需要异二聚化。截短诱变揭示突触蛋白Ia通过包括域B，C和E在内的分布式结合位点进行靶向。尽管域A对于靶向作用不是必需的，但其存在增强了靶向作用。域D抑制了靶向作用，但域E克服了这种抑制作用。因此，突触素需要多种分子间和分子内相互作用才能靶向突触前末端。

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