Cell-Specific Transcriptional Profiling of Ciliated Sensory Neurons Reveals Regulators of Behavior and Extracellular Vesicle Biogenesis.
Cell-Specific Transcriptional Profiling of Ciliated Sensory Neurons Reveals Regulators of Behavior and Extracellular Vesicle Biogenesis.
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DOI：
10.1016/j.cub.2015.10.057
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发表时间：
2015-12-21
期刊：
影响因子：
--
通讯作者：
Barr MM
中科院分区：
文献类型：
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作者：
Wang J;Kaletsky R;Silva M;Williams A;Haas LA;Androwski RJ;Landis JN;Patrick C;Rashid A;Santiago-Martinez D;Gravato-Nobre M;Hodgkin J;Hall DH;Murphy CT;Barr MM
纤毛和细胞外囊泡 (EV) 是信号细胞器。纤毛充当细胞的感觉触角，其缺陷会导致人类纤毛病。纤毛既释放电动汽车又与电动汽车结合。 EV 是细胞释放的亚微米大小的颗粒，在短程和长程细胞间通讯中发挥作用。在秀丽隐杆线虫和哺乳动物中，常染色体显性多囊肾病 (ADPKD) 基因产物多囊蛋白-1 和多囊蛋白-2 定位于纤毛和 EV，以相同的遗传途径发挥作用，并以感觉能力发挥作用，这表明古老的保守性。目前缺乏对 EV 生物学以及多囊蛋白、纤毛和 EV 之间关系的基本了解。为了定义纤毛 EV 释放细胞的特性，我们对从成年秀丽隐杆线虫中分离出的 27 个 GFP 标记的 EV 释放神经元 (EVN) 进行了 RNAseq。我们鉴定了 335 个显着过度表达的基因，其中 61 个由 GFP 报告基因验证。 EVN 转录谱揭示了控制 EV 生物发生和多囊蛋白信号传导的新途径，还鉴定了 EV 货物，其中包括抗菌肽和 ASIC 通道。肿瘤坏死相关因子 (TRAF) 同源物 trf-1 和 trf-2 以及 p38 丝裂原激活蛋白激酶 (MAPK) pmk-1 在控制雄性交配行为的多囊蛋白信号通路中发挥作用。 pmk-1 也是 EV 生物发生所必需的，独立于先天免疫 MAPK 信号级联。从成年动物中分离出的纤毛感觉神经元亚型的第一个高分辨率转录组图谱揭示了 EVN 的功能成分。
Cilia and extracellular vesicles (EVs) are signaling organelles. Cilia act as cellular sensory antennae, with defects resulting in human ciliopathies. Cilia both release and bind to EVs. EVs are submicron-sized particles released by cells and function in both short and long range intercellular communication. In C. elegans and mammals, the Autosomal Dominant Polycystic Kidney Disease (ADPKD) gene products polycystin-1 and polycystin-2 localize to both cilia and EVs, act in the same genetic pathway, and function in a sensory capacity, suggesting ancient conservation. A fundamental understanding of EV biology and the relationship between the polycystins, cilia, and EVs is lacking. To define properties of a ciliated EV-releasing cell, we performed RNAseq on 27 GFP-labeled EV releasing neurons (EVNs) isolated from adult C. elegans. We identified 335 significantly overrepresented genes, of which 61 were validated by GFP reporters. The EVN transcriptional profile uncovered new pathways controlling EV biogenesis and polycystin signaling and also identified EV cargo, which included an antimicrobial peptide and ASIC channel. Tumor necrosis associated factor (TRAF) homologues trf-1 and trf-2 and the p38 mitogen-activated protein kinase (MAPK) pmk-1 acted in polycystin signaling pathways controlling male mating behaviors. pmk-1 was also required for EV biogenesis, independent of the innate immunity MAPK signaling cascade. This first high-resolution transcriptome profile of a subtype of ciliated sensory neurons isolated from adult animals reveals the functional components of an EVN.