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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A peptide zipcode sufficient for anterograde transport within amyloid precursor protein
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A peptide zipcode sufficient for anterograde transport within amyloid precursor protein

机译：足以在淀粉样前体蛋白内进行顺行转运的肽邮政编码

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摘要

Fast anterograde transport of membrane-bound organelles delivers molecules synthesized in the neuronal cell body outward to distant synapses. Identification of the molecular "zipcodes" on organelles that mediate attachment and activation of microtubule-based motors for this directed transport is a major area of inquiry. Here we identify a short peptide sequence (15 aa) from the cytoplasmic C terminus of amyloid precursor protein (APP-C) sufficient to mediate the anterograde transport of peptide-conjugated beads in the squid giant axon. APP-C beads travel at fast axonal transport rates (0.53 mu m/s average velocity, 0.9 mu m/s maximal velocity) whereas beads coupled to other peptides coinjected into the same axon remain stationary at the injection site. This transport appears physiologic, because it mimics behavior of endogenous squid organelles and of beads conjugated to C99, a polypeptide containing the full-length cytoplasmic domain of amyloid precursor protein (APP). Beads conjugated to APP lacking the APP-C domain are not transported. Coinjection of APP-C peptide reduces C99 bead motility by 75% and abolishes APP-C bead motility, suggesting that the soluble peptide competes with protein-conjugated beads for axoplasmic motor(s). The APP-C domain is conserved (13/15 aa) from squid to human, and peptides from either squid or human APP behave similarly. Thus, we have identified a conserved peptide zipcode sufficient to direct anterograde transport of exogenous cargo and suggest that one of APP's roles may be to recruit and activate axonal machinery for endogenous cargo transport.
机译：膜结合细胞器的快速顺行转运将神经元细胞体内合成的分子向外传递至遥远的突触。识别介导基于微管的马达的附着和激活以进行这种定向运输的细胞器上的分子“邮政编码”是研究的主要领域。在这里，我们从淀粉样前体蛋白（APP-C）的细胞质C末端确定了一个短肽序列（15 aa），足以介导鱿鱼巨轴突中肽共轭珠的顺行转运。 APP-C磁珠以快速的轴突运输速度（平均速度为0.53μm/ s，最大速度为0.9μm/ s）移动，而与共注射到同一轴突中的其他肽偶联的磁珠则在注射部位保持静止。这种转运似乎是生理性的，因为它模拟了内源性鱿鱼细胞器和与C99结合的珠子的行为，C99是含有淀粉样前体蛋白（APP）全长胞质域的多肽。与缺少APP-C域的APP缀合的珠子不会被运输。共注射APP-C肽可将C99珠子的运动性降低75％，并消除APP-C珠子的运动性，这表明可溶性肽与蛋白缀合的珠子竞争轴质运动。鱿鱼到人的APP-C结构域是保守的（13/15氨基酸），鱿鱼或人APP的肽的行为相似。因此，我们确定了足以指导外源货物顺行运输的保守肽邮政编码，并提出APP的作用之一可能是招募和激活用于内源货物运输的轴突机器。

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