DHHC4 and DHHC5 Facilitate Fatty Acid Uptake by Palmitoylating and Targeting CD36 to the Plasma Membrane
DHHC4 and DHHC5 Facilitate Fatty Acid Uptake by Palmitoylating and Targeting CD36 to the Plasma Membrane
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DHHC4 和 DHHC5 通过棕榈酰化和将 CD36 靶向质膜来促进脂肪酸摄取
DOI：
10.1016/j.celrep.2018.12.022
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发表时间：
2019
期刊：
影响因子：
8.8
通讯作者：
Zhao Tong-Jin
中科院分区：
文献类型：
--
作者：
Wang Juan;Hao Jian-Wei;Wang Xu;Guo Huiling;Sun Hui-Hui;Lai Xiao-Ying;Liu Li-Ying;Zhu Mingxia;Wang Hao-Yan;Li Yi-Fan;Yu Li-Yang;Xie Changchuan;Wang Hong-Rui;Mo Wei;Zhou Hai-Meng;Chen Shuai;Liang Guosheng;Zhao Tong-Jin
脂肪酸摄取是脂肪酸利用的第一步，但目前尚不清楚该过程是如何调节的。蛋白质棕榈酰化是一种脂肪酰基修饰，在蛋白质靶向和运输中发挥着关键的调节作用；然而，其调节脂肪酸代谢的功能尚不清楚。在这里，我们发现两种含有 Asp-His-His-Cys (DHHC) 基序的棕榈酰酰基转移酶 DHHC4 和 DHHC5 调节脂肪酸的摄取。 DHHC4 和 DHHC5 在不同的亚细胞定位中发挥作用，控制清道夫受体 CD36 的棕榈酰化、质膜定位和脂肪酸摄取活性。细胞中 DHHC4 或 DHHC5 的耗尽会破坏 CD36 依赖性脂肪酸的摄取。此外，Dhhc4−/−和脂肪特异性Dhhc5基因敲除小鼠均表现出脂肪组织中脂肪酸摄取活性降低，并在急性寒冷暴露后出现严重体温过低。这些发现证明 DHHC4 和 DHHC5 在调节脂肪酸摄取中发挥着关键作用。
Fatty acid uptake is the first step in fatty acid utilization, but it remains unclear how the process is regulated. Protein palmitoylation is a fatty acyl modification that plays a key regulatory role in protein targeting and trafficking; however, its function in regulating fatty acid metabolism is unknown. Here, we show that two of the Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferases, DHHC4 and DHHC5, regulate fatty acid uptake. DHHC4 and DHHC5 function at different subcellular localizations to control the palmitoylation, plasma membrane localization, and fatty acid uptake activity of the scavenger receptor CD36. Depletion of either DHHC4 or DHHC5 in cells disrupts CD36-dependent fatty acid uptake. Furthermore, bothDhhc4−/−and adipose-specificDhhc5knockout mice show decreased fatty acid uptake activity in adipose tissues and develop severe hypothermia upon acute cold exposure. These findings demonstrate a critical role of DHHC4 and DHHC5 in regulating fatty acid uptake.