Endocytic trafficking of sphingomyelin depends on its acyl chain length
Endocytic trafficking of sphingomyelin depends on its acyl chain length
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DOI：
10.1091/mbc.e07-04-0330
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发表时间：
2007-12-01
影响因子：
3.3
通讯作者：
Ikonen, Elina
中科院分区：
文献类型：
--
作者：
Koivusalo, Mirkka;Jansen, Maurice;Ikonen, Elina
为了研究内吞脂质运输的原理，我们将具有不同酰基链长度和结构域分区特性的芘鞘磷脂（PyrSMs）引入人成纤维细胞或HeLa细胞中。我们发现，一个长链，有序的结构域偏好PyrSM的靶向Hrs和Tsg 101依赖性晚期内体室和循环到质膜的NPC 1和胆固醇依赖性的方式。一个短链，无序的结构域更有效地回收利用PyrSM，通过使用Hrs-，Tsg 101-和NPC 1-独立的路由，是不敏感的胆固醇负荷。未标记的鞘磷脂（SM）观察到类似的链长依赖性回收。这些发现1）确立酰基链长度作为SM内吞运输的重要决定因素，2）将ESCRT复合物蛋白和NPC 1与有序结构域脂质到质膜的内吞再循环有关，3）引入长链PyrSM作为追踪该途径的第一个荧光脂质。
To study the principles of endocytic lipid trafficking, we introduced pyrene sphingomyelins (PyrSMs) with varying acyl chain lengths and domain partitioning properties into human fibroblasts or HeLa cells. We found that a long-chain, ordered-domain preferring PyrSM was targeted Hrs and Tsg101 dependently to late endosomal compartments and recycled to the plasma membrane in an NPC1- and cholesterol-dependent manner. A short-chain, disordered domain preferring PyrSM recycled more effectively, by using Hrs-, Tsg101- and NPC1-independent routing that was insensitive to cholesterol loading. Similar chain length-dependent recycling was observed for unlabeled sphingomyelins (SMs). The findings 1) establish acyl chain length as an important determinant in the endocytic trafficking of SMs, 2) implicate ESCRT complex proteins and NPC1 in the endocytic recycling of ordered domain lipids to the plasma membrane, and 3) introduce long-chain PyrSM as the first fluorescent lipid tracing this pathway.