A role for ubiquitin ligases and Spartin/SPG20 in lipid droplet turnover.
A role for ubiquitin ligases and Spartin/SPG20 in lipid droplet turnover.
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DOI：
10.1083/jcb.200808041
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发表时间：
2009-03-23
期刊：
影响因子：
--
通讯作者：
Bieniasz PD
中科院分区：
文献类型：
--
作者：
Eastman SW;Yassaee M;Bieniasz PD
HECT（与E6AP C末端同源）泛素连接酶在真核细胞中具有多种功能。在筛选与HECT泛素连接酶WWP1结合的蛋白质时，我们鉴定了Spartin，也称为SPG20。这种蛋白质在神经系统疾病Troyer综合征中被截短。在这项研究中，我们发现SPG20与脂滴（LDs）表面相关，并可以调节其大小和数量。SPG20与另一种LD蛋白TIP47结合，并且两种蛋白质与另外的LD蛋白、亲脂蛋白/脂肪细胞分化相关蛋白竞争LD的占用。Troyer综合征中存在的突变SPG20不具有这些活性。使用RNA干扰消耗SPG20增加了当细胞用油酸喂养时LD的数量和大小。WWP1与SPG20的结合和随后的泛素转移从LD中去除SPG20并降低共表达的SPG20的水平。这些实验表明泛素连接酶和SPG20在调节LD周转和Troyer综合征的潜在病理机制中的功能。
HECT (homologous to the E6AP C terminus) ubiquitin ligases have diverse functions in eukaryotic cells. In screens for proteins that bind to the HECT ubiquitin ligase WWP1, we identified Spartin, which is also known as SPG20. This protein is truncated in a neurological disease, Troyer syndrome. In this study, we show that SPG20 associates with the surface of lipid droplets (LDs) and can regulate their size and number. SPG20 binds to another LD protein, TIP47, and both proteins compete with an additional LD protein, adipophilin/adipocyte differentiation-related protein, for occupancy of LDs. The mutant SPG20 present in Troyer syndrome does not possess these activities. Depletion of SPG20 using RNA interference increases the number and size of LDs when cells are fed with oleic acid. Binding of WWP1 to SPG20 and the consequent ubiquitin transfer remove SPG20 from LDs and reduce the levels of coexpressed SPG20. These experiments suggest functions for ubiquitin ligases and SPG20 in the regulation of LD turnover and potential pathological mechanisms in Troyer syndrome.
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