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树突状细胞的外泌体分泌受 Hrs 调控,Hrs 是一种 ESCRT-0 蛋白。

Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein.

机构信息

Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.

出版信息

Biochem Biophys Res Commun. 2010 Aug 27;399(3):384-90. doi: 10.1016/j.bbrc.2010.07.083. Epub 2010 Jul 29.

Abstract

Exosomes are nanovesicles derived from multivesicular bodies (MVBs) in antigen-presenting cells. The components of the ESCRT (endosomal sorting complex required for transport) pathway are critical for the formation of MVBs, however the relationship between the ESCRT pathway and the secretion of exosomes remains unclear. We here demonstrate that Hrs, an ESCRT-0 protein, is required for fascilitating the secretion of exosomes in dendritic cells (DCs). Ultrastructural analyses showed typical saucer-shaped exosomes in the culture supernatant from both the control and Hrs-depleted DCs. However, the amount of exosome secretion was significantly decreased in Hrs-depleted DCs following stimulations with ovalbumin (OVA) as well as calcium ionophore. Antigen-presentation activity was also suppressed in exsosomes purified from Hrs-depleted DCs, while no alteration in OVA degradation was seen in Hrs-depleted DCs. These data indicated that Hrs is involved in the regulation of antigen-presentation activity through the exosome secretion.

摘要

外泌体是源自抗原呈递细胞的多泡体(MVBs)的纳米囊泡。参与内体分选复合物(ESCRT)途径的成分对于 MVBs 的形成至关重要,然而 ESCRT 途径与外泌体的分泌之间的关系仍不清楚。我们在此证明,ESCRT-0 蛋白 Hrs 对于促进树突状细胞(DC)中外泌体的分泌是必需的。超微结构分析显示,对照组和 Hrs 耗尽的 DC 的培养上清液中均存在典型的碟形外泌体。然而,在用卵清蛋白(OVA)和钙离子载体刺激后,Hrs 耗尽的 DC 中外泌体的分泌量显著减少。从 Hrs 耗尽的 DC 中纯化的外泌体的抗原呈递活性也受到抑制,而在 Hrs 耗尽的 DC 中未见 OVA 降解的改变。这些数据表明 Hrs 通过外泌体的分泌参与调节抗原呈递活性。

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