Protein composition of axonal dopamine release sites in the striatum.
Protein composition of axonal dopamine release sites in the striatum.
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DOI：
10.7554/elife.83018
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发表时间：
2022-12-29
期刊：
影响因子：
7.7
通讯作者：
Kaeser, Pascal S.
中科院分区：
文献类型：
--
作者：
Kershberg, Lauren;Banerjee, Aditi;Kaeser, Pascal S.
多巴胺是认知和运动的重要调节剂。我们最近发现，诱发的多巴胺分泌是快速的，并依赖于活跃的区域样释放位点。在这里，我们使用体内生物素识别（iBioID）接近蛋白质组学在小鼠纹状体，以评估哪些蛋白质存在于这些网站。使用三个释放位点诱饵，我们确定了富集在一般多巴胺轴突蛋白质含量的蛋白质，它们分为几类，包括活性区，Ca 2+调节和突触囊泡蛋白。我们还检测到许多蛋白质以前没有与囊泡胞吐。敲除突触前组织者蛋白RIM强烈降低了iBioID获得的命中数，而Synaptotagmin-1敲除则没有。α-突触核蛋白是一种与帕金森病相关的蛋白质，在释放位点富集，并且在两种测试的突变体中其富集都丧失了。我们的结论是RIM组织支架多巴胺释放网站，并提供这些网站的组成的蛋白质组学评估。
Dopamine is an important modulator of cognition and movement. We recently found that evoked dopamine secretion is fast and relies on active zone-like release sites. Here, we used in vivo biotin identification (iBioID) proximity proteomics in mouse striatum to assess which proteins are present at these sites. Using three release site baits, we identified proteins that are enriched over the general dopamine axonal protein content, and they fell into several categories, including active zone, Ca2+ regulatory, and synaptic vesicle proteins. We also detected many proteins not previously associated with vesicular exocytosis. Knockout of the presynaptic organizer protein RIM strongly decreased the hit number obtained with iBioID, while Synaptotagmin-1 knockout did not. α-Synuclein, a protein linked to Parkinson’s disease, was enriched at release sites, and its enrichment was lost in both tested mutants. We conclude that RIM organizes scaffolded dopamine release sites and provide a proteomic assessment of the composition of these sites.