Evidences against vesicle-dependent trafficking and involvement of extracellular proteasomes into cell-to-cell communications
Evidences against vesicle-dependent trafficking and involvement of extracellular proteasomes into cell-to-cell communications
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DOI：
10.1016/j.bbrc.2018.11.152
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发表时间：
2019-01-08
影响因子：
3.1
通讯作者：
Tsimokha, Anna S.
中科院分区：
文献类型：
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作者：
Diakonov, Egor E.;Selenina, Anastasiia V.;Tsimokha, Anna S.
泛素蛋白酶体系统参与了细胞内最基本的过程的调节，该系统的失调可导致某些类型的人类疾病。该系统的蛋白水解核心，20S蛋白酶体，已在健康人和患有各种炎症、自身免疫和肿瘤疾病的患者的生理液体中发现。已发现这些细胞外蛋白酶体的浓度与疾病状态相关，具有预后意义。然而，这些蛋白酶体的转运机制和功能在很大程度上还不清楚。以往的研究表明，胞外蛋白酶体的转运可能通过微囊泡和exosomes进行，从而提出了胞外蛋白酶体参与细胞间通讯的假说。在这里，我们表明，微泡和外来体，两种主要的已知类型的细胞间的车辆，不包含可检测的蛋白酶体。此外，无论是亲和纯化的还是由供体细胞自然释放到条件培养基中的20S蛋白酶体都不能穿透受体HeLa细胞。两者合计，这些结果表明，细胞外蛋白酶体不太可能参与细胞间的通信，它们的释放由细胞服务于其他生物学目的。(C)2018爱思唯尔公司All rights reserved.
The ubiquitin proteasome system is involved in the regulation of most basic intracellular processes, and deregulation of this system can results in certain kinds of human diseases. Proteolytic core this system, the 20S proteasome, has been found in physiological fluids of both healthy humans and patients suffering from a variety of inflammatory, autoimmune, and neoplastic diseases. The concentration of these extracellular proteasomes has been found to correlate with the diseased state, being of a prognostic significance. The transport mechanisms and functions of these proteasomes, however, are largely unclear. Previous studies revealed that the transport of extracellular proteasomes may occur via microvesicles and exosomes, which led to the hypothesis that extracellular proteasomes are implicated in cellto-cell communication process. Here we show that microvesicles and exosomes, two major known types of intercellular vehicles, contain no detectable proteasomes. Moreover, neither affinity purified nor naturally released into conditioned medium by donor cells 20S proteasomes could penetrate recipient HeLa cells. Taken together, these results suggest that extracellular proteasomes are unlikely to be involved in the cell-to-cell communication and that their release by cells serve other biological purposes. (C) 2018 Elsevier Inc. All rights reserved.