Plasma membrane-derived extracellular microvesicles mediate non-canonical intercellular NOTCH signaling.
Plasma membrane-derived extracellular microvesicles mediate non-canonical intercellular NOTCH signaling.
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DOI：
10.1038/s41467-017-00767-2
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发表时间：
2017-09-27
影响因子：
16.6
通讯作者：
Lu Q
中科院分区：
文献类型：
--
作者：
Wang Q;Lu Q
ARMMS(arrestin Domaining Protein 1，ARRDC1)介导的微泡是直接在质膜上发芽的胞外小泡，但对这些小泡的分子组成和生理功能知之甚少。在这里，我们报告ARMMS含有活性的Noch受体，并介导非规范的细胞间Notch信号。我们鉴定了100多种显著富含ARMMS的蛋白质，包括ARRDC1、TSG101和多个ESCRT复合蛋白。大约三分之一的ARMMS富集蛋白是质膜蛋白，包括NOTCH2受体。NOTCH2被分泌到ARMMS中的ITCH E3连接酶和金属蛋白酶ADAM10所促进。ARMMS中的Notch2可以被传递到受体细胞中，并被γ分泌酶切割激活，诱导Notch特异的基因表达。综上所述，我们的发现揭示了ARMMS在一种新的缺口信号通路中的作用，该通路作用于距离，并且独立于细胞间的直接接触。ARMMS是直接在质膜上发芽的细胞外小泡，其功能尚不清楚。作者对ARMMS的蛋白质组分进行了纯化和蛋白质组学分析，结果表明，ARMMS中的Noch受体被招募到ARMMS中，并可以转移到受体细胞中介导Noch信号转导。
ARMMs (arrestin domain-containing protein 1 (ARRDC1)-mediated microvesicles) are extracellular vesicles that bud directly at the plasma membrane; however, little is known about the molecular composition and physiological function of these vesicles. Here we report that ARMMs contain active NOTCH receptors and mediate a non-canonical intercellular NOTCH signaling. We identify over 100 proteins that are significantly enriched in ARMMs, including ARRDC1, TSG101 and multiple ESCRT complex proteins. About a third of ARMMs-enriched proteins are plasma membrane proteins, including the NOTCH2 receptor. The incorporation of NOTCH2 into ARMMs is facilitated by the ITCH E3 ligase and the metalloprotease ADAM10, both of which are also secreted into ARMMs. NOTCH2 in ARMMs can be delivered into recipient cells, and upon activation by γ-secretase cleavage, induces NOTCH-specific gene expression. Together, our findings reveal a role for ARMMs in a novel NOTCH signaling pathway that acts in distance and is independent of direct cell–cell contact. ARMMs are extracellular vesicles that bud directly at the plasma membrane; their function is poorly understood. Here the authors purify and carryout a proteomics analysis of the protein components of ARMMs, and show that NOTCH receptors are recruited into ARMMs and can be transferred to recipient cells to mediate NOTCH signaling.
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影响因子：
4.8
作者：
Qiu, L;Joazeiro, C;Liu, YC
通讯作者：
Liu, YC
DOI：
10.1038/nri3622
发表时间：
2014-03
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.1200448109
发表时间：
2012-03-13
影响因子：
11.1
作者：
Nabhan, Joseph F.;Hu, Ruoxi;Lu, Quan
通讯作者：
Lu, Quan
影响因子：
14.9
作者：
Mathivanan S;Fahner CJ;Reid GE;Simpson RJ
通讯作者：
Simpson RJ
影响因子：
21.3
作者：
Skog, Johan;Wuerdinger, Tom;van Rijn, Sjoerd;Meijer, Dimphna H.;Gainche, Laura;Sena-Esteves, Miguel;Curry, William T., Jr.;Carter, Bob S.;Krichevsky, Anna M.;Breakefield, Xandra O.
通讯作者：
Breakefield, Xandra O.