Extracellular vesicles direct migration by synthesizing and releasing chemotactic signals.
Extracellular vesicles direct migration by synthesizing and releasing chemotactic signals.
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DOI：
10.1083/jcb.201710170
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发表时间：
2018-08-06
期刊：
影响因子：
--
通讯作者：
Parent CA
中科院分区：
文献类型：
--
作者：
Kriebel PW;Majumdar R;Jenkins LM;Senoo H;Wang W;Ammu S;Chen S;Narayan K;Iijima M;Parent CA
Kriebel等人。研究表明，网柄菌细胞释放胞外小泡(EVS)，这些囊泡不仅含有趋化因子cAMP，还能主动合成和释放cAMP以促进趋化作用。结果表明，EV对cAMP的释放是由ABCC8转运体介导的。趋化信号通过分泌额外的趋化物质传递给邻近的细胞。我们先前在盘基网眼菌中发现，合成趋化物质环腺苷一磷酸(CAMP)的腺酰环化酶A存在于在细胞背面聚集的多囊泡体(MVB)的腔内小泡中。利用超微结构重建，我们现在表明，含有ACA的MVB释放其内容物以吸引邻近细胞。我们表明，释放的囊泡能够引导迁移和流动，并且是趋化信号传递的中心。我们证明，释放的囊泡不仅含有cAMP，而且可以主动合成和释放cAMP来促进趋化作用。通过蛋白质组学、药理学和遗传学方法，我们确定囊泡cAMP是通过ABCC8转运体释放的。综上所述，我们的发现表明，盘藻细胞释放的胞外小泡是在趋化和流动过程中介导信号传递的功能实体。
Kriebel et al. show that Dictyostelium cells release extracellular vesicles (EVs) that not only contain the chemoattractant cAMP but also actively synthesize and release cAMP to promote chemotaxis. They show that the EV release of cAMP is mediated by the ABCC8 transporter. Chemotactic signals are relayed to neighboring cells through the secretion of additional chemoattractants. We previously showed in Dictyostelium discoideum that the adenylyl cyclase A, which synthesizes the chemoattractant cyclic adenosine monophosphate (cAMP), is present in the intraluminal vesicles of multivesicular bodies (MVBs) that coalesce at the back of cells. Using ultrastructural reconstructions, we now show that ACA-containing MVBs release their contents to attract neighboring cells. We show that the released vesicles are capable of directing migration and streaming and are central to chemotactic signal relay. We demonstrate that the released vesicles not only contain cAMP but also can actively synthesize and release cAMP to promote chemotaxis. Through proteomic, pharmacological, and genetic approaches, we determined that the vesicular cAMP is released via the ABCC8 transporter. Together, our findings show that extracellular vesicles released by D. discoideum cells are functional entities that mediate signal relay during chemotaxis and streaming.
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影响因子：
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通讯作者：
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