Neutral sphingomyelinases control extracellular vesicles budding from the plasma membrane.

Neutral sphingomyelinases control extracellular vesicles budding from the plasma membrane.
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中性鞘磷脂酶调控从质膜出芽产生的细胞外囊泡。

DOI:
10.1080/20013078.2017.1378056
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发表时间:
2017
影响因子:
16
通讯作者:
Gross JC
Gross JC
中科院分区:
医学2区
文献类型:
--
作者:
Menck K;Sönmezer C;Worst TS;Schulz M;Dihazi GH;Streit F;Erdmann G;Kling S;Boutros M;Binder C;Gross JC

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细胞外囊泡(EVs)是由细胞分泌到所有体液中的膜颗粒。几个EV种群在大小和细胞起源上存在差异。通过差速离心,14000 g(“微囊泡”(MV))和100000 g(“外泌体”)的ev颗粒可以通过蛋白质标记进行区分。中性鞘磷脂酶(nSMase)抑制已被证明可以抑制细胞外泌体的释放,并已被用于研究其功能意义。nsmase(也称为SMPD2和SMPD3)如何影响mv的基础分泌尚不清楚。在这里,我们研究了SMPD2/3如何影响两个EV种群。GW4869或RNAi抑制SMPD2/3会减少外泌体的分泌,但也会增加质膜上的mv分泌。两个种群在代谢物组成上存在显著差异,在这些条件下,Wnt蛋白被特异性地装载到mv上。综上所述,我们的数据揭示了SMPD2/3在质膜囊泡出芽中的一种新的调控功能,并清楚地表明,尽管囊泡的生物发生方式不同,但囊泡输出的途径是可适应的。
Extracellular vesicles (EVs) are membrane particles secreted from cells into all body fluids. Several EV populations exist differing in size and cellular origin. Using differential centrifugation EVs pelleting at 14,000 g (“microvesicles” (MV)) and 100,000 g (“exosomes”) are distinguishable by protein markers. Neutral sphingomyelinase (nSMase) inhibition has been shown to inhibit exosome release from cells and has since been used to study their functional implications. How nSMases (also known as SMPD2 and SMPD3) affect the basal secretion of MVs is unclear. Here we investigated how SMPD2/3 impact both EV populations. SMPD2/3 inhibition by GW4869 or RNAi decreases secretion of exosomes, but also increases secretion of MVs from the plasma membrane. Both populations differ significantly in metabolite composition and Wnt proteins are specifically loaded onto MVs under these conditions. Taken together, our data reveal a novel regulatory function of SMPD2/3 in vesicle budding from the plasma membrane and clearly suggest that – despite the different vesicle biogenesis – the routes of vesicular export are adaptable.
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