Eliaz Dror, Kannan Sriram, Shaked Hadassa, Arvatz Gil, Tkacz Itai Dov, Binder Lior, Waldman Ben-Asher Hiba, Okalang Uthman, Chikne Vaibhav, Cohen-Chalamish Smadar, Michaeli Shulamit
The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan Israel.
PLoS Pathog. 2017 Mar 3;13(3):e1006245. doi: 10.1371/journal.ppat.1006245. eCollection 2017 Mar.
Extracellular vesicles (EV) secreted by pathogens function in a variety of biological processes. Here, we demonstrate that in the protozoan parasite Trypanosoma brucei, exosome secretion is induced by stress that affects trans-splicing. Following perturbations in biogenesis of spliced leader RNA, which donates its spliced leader (SL) exon to all mRNAs, or after heat-shock, the SL RNA is exported to the cytoplasm and forms distinct granules, which are then secreted by exosomes. The exosomes are formed in multivesicular bodies (MVB) utilizing the endosomal sorting complexes required for transport (ESCRT), through a mechanism similar to microRNA secretion in mammalian cells. Silencing of the ESCRT factor, Vps36, compromised exosome secretion but not the secretion of vesicles derived from nanotubes. The exosomes enter recipient trypanosome cells. Time-lapse microscopy demonstrated that cells secreting exosomes or purified intact exosomes affect social motility (SoMo). This study demonstrates that exosomes are delivered to trypanosome cells and can change their migration. Exosomes are used to transmit stress signals for communication between parasites.
病原体分泌的细胞外囊泡（EV）在多种生物学过程中发挥作用。在此，我们证明在原生动物寄生虫布氏锥虫中，外泌体分泌是由影响反式剪接的应激诱导的。在剪接前导RNA的生物合成受到干扰后（剪接前导RNA将其剪接前导（SL）外显子捐赠给所有mRNA），或在热休克后，SL RNA被输出到细胞质并形成不同的颗粒，然后这些颗粒由外泌体分泌。外泌体在多泡体（MVB）中利用运输所需的内体分选复合物（ESCRT）形成，其机制类似于哺乳动物细胞中微小RNA的分泌。ESCRT因子Vps36的沉默损害了外泌体的分泌，但不影响源自纳米管的囊泡的分泌。外泌体进入受体锥虫细胞。延时显微镜显示，分泌外泌体的细胞或纯化的完整外泌体影响群体运动性（SoMo）。这项研究表明，外泌体被递送至锥虫细胞并可改变其迁移。外泌体用于传递应激信号以在寄生虫之间进行通信。
