Active endocannabinoids are secreted on extracellular membrane vesicles
Active endocannabinoids are secreted on extracellular membrane vesicles
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DOI：
10.15252/embr.201439668
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发表时间：
2015-02-01
期刊：
影响因子：
7.7
通讯作者：
Verderio, Claudia
中科院分区：
文献类型：
--
作者：
Gabrielli, Martina;Battista, Natalia;Verderio, Claudia
内源性大麻素主要影响神经系统内的神经元突触通讯。为了发挥其功能，内源性大麻素需要穿过细胞间隙。然而，疏水性内源性大麻素如何穿过细胞膜并在细胞外移动仍然是一个未解决的问题。在这里，我们表明，内源性大麻素分泌通过小胶质细胞产生的细胞外膜囊泡。我们证明，小胶质细胞外囊泡进行其表面N-花生四烯酸乙醇胺（AEA），这是能够刺激1型大麻素受体（CB 1），并抑制突触前传递，在目标GABA能神经元。这是内源性大麻素的细胞外囊泡运输的功能作用的第一个证明。
Endocannabinoids primarily influence neuronal synaptic communication within the nervous system. To exert their function, endocannabinoids need to travel across the intercellular space. However, how hydrophobic endocannabinoids cross cell membranes and move extracellularly remains an unresolved problem. Here, we show that endocannabinoids are secreted through extracellular membrane vesicles produced by microglial cells. We demonstrate that microglial extracellular vesicles carry on their surface N-arachidonoylethanolamine (AEA), which is able to stimulate type-1 cannabinoid receptors (CB1), and inhibit presynaptic transmission, in target GABAergic neurons. This is the first demonstration of a functional role of extracellular vesicular transport of endocannabinoids.