Wang Juan, Silva Malan, Haas Leonard A, Morsci Natalia S, Nguyen Ken C Q, Hall David H, Barr Maureen M
Department of Genetics and The Human Genetics Institute of New Jersey, Rutgers University, 145 Bevier Road, Piscataway, NJ 08854, USA.
Center for C. elegans Anatomy, Albert Einstein College of Medicine, 1410 Pelham Parkway, Bronx, NY 10461, USA.
Curr Biol. 2014 Mar 3;24(5):519-25. doi: 10.1016/j.cub.2014.01.002. Epub 2014 Feb 13.
Cells release extracellular vesicles (ECVs) that play important roles in intercellular communication and may mediate a broad range of physiological and pathological processes. Many fundamental aspects of ECV biogenesis and signaling have yet to be determined, with ECV detection being a challenge and obstacle due to the small size (100 nm) of the ECVs. We developed an in vivo system to visualize the dynamic release of GFP-labeled ECVs. We show here that specific Caenorhabdidits elegans ciliated sensory neurons shed and release ECVs containing GFP-tagged polycystins LOV-1 and PKD-2. These ECVs are also abundant in the lumen surrounding the cilium. Electron tomography and genetic analysis indicate that ECV biogenesis occurs via budding from the plasma membrane at the ciliary base and not via fusion of multivesicular bodies. Intraflagellar transport and kinesin-3 KLP-6 are required for environmental release of PKD-2::GFP-containing ECVs. ECVs isolated from wild-type animals induce male tail-chasing behavior, while ECVs isolated from klp-6 animals and lacking PKD-2::GFP do not. We conclude that environmentally released ECVs play a role in animal communication and mating-related behaviors.
细胞释放细胞外囊泡(ECV),其在细胞间通讯中发挥重要作用,并可能介导广泛的生理和病理过程。ECV生物发生和信号传导的许多基本方面尚未确定,由于ECV尺寸小(100纳米),ECV检测是一项挑战和障碍。我们开发了一种体内系统来可视化绿色荧光蛋白(GFP)标记的ECV的动态释放。我们在此表明,特定的秀丽隐杆线虫纤毛感觉神经元脱落并释放含有GFP标记的多囊蛋白LOV-1和PKD-2的ECV。这些ECV在纤毛周围的管腔中也很丰富。电子断层扫描和遗传分析表明,ECV生物发生是通过在纤毛基部从质膜出芽而不是通过多囊泡体的融合发生的。鞭毛内运输和驱动蛋白-3 KLP-6是含PKD-2::GFP的ECV环境释放所必需的。从野生型动物分离的ECV诱导雄性追尾行为,而从klp-6动物分离且缺乏PKD-2::GFP的ECV则不会。我们得出结论,环境释放的ECV在动物通讯和交配相关行为中起作用。