Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes
Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes
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DOI：
10.1038/ncomms3712
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发表时间：
2013-11-01
影响因子：
16.6
通讯作者：
Nakamura, Shun-ichi
中科院分区：
文献类型：
--
作者：
Kajimoto, Taketoshi;Okada, Taro;Nakamura, Shun-ichi
在核内体成熟后期，货物分子被分类到多泡核内体（MVEs）的腔内囊泡（ILVs）中，并被递送到溶酶体降解或与质膜融合以释放外泌体。外泌体ilv的形成机制和货物分选为ilv以释放外泌体的机制尚不清楚。在这里，我们发现抑制G蛋白（Gi）偶联鞘氨醇1-磷酸（S1P）受体调节外泌体MVE成熟。MVEs上的gi偶联S1P受体通过细胞器内的自分泌激活持续供应S1P而组成性激活。我们还发现，MVEs上的gi偶联S1P受体的持续激活对于货物分选到用于外泌体释放的ilv至关重要。我们的研究结果揭示了不依赖escrt的外泌体MVEs成熟的机制。
During late endosome maturation, cargo molecules are sorted into intralumenal vesicles (ILVs) of multivesicular endosomes (MVEs), and are either delivered to lysosomes for degradation or fused with the plasma membranes for exosome release. The mechanism underlying formation of exosomal ILVs and cargo sorting into ILVs destined for exosome release is still unclear. Here we show that inhibitory G protein (Gi)-coupled sphingosine 1-phosphate (S1P) receptors regulate exosomal MVE maturation. Gi-coupled S1P receptors on MVEs are constitutively activated through a constant supply of S1P via autocrine activation within organelles. We also found that the continuous activation of Gi-coupled S1P receptors on MVEs is essential for cargo sorting into ILVs destined for exosome release. Our results reveal a mechanism underlying ESCRT-independent maturation of exosomal MVEs.