DHHC4 and DHHC5 Facilitate Fatty Acid Uptake by Palmitoylating and Targeting CD36 to the Plasma Membrane

Juan Wang; Jian Wei Hao; Xu Wang; Huiling Guo; Hui Hui Sun; Xiao Ying Lai; Li Ying Liu; Mingxia Zhu; Hao Yan Wang; Yi Fan Li; Li Yang Yu; Changchuan Xie; Hong Rui Wang; Wei Mo; Hai Meng Zhou; Shuai Chen; Guosheng Liang; Tong Jin Zhao

doi:10.1016/j.celrep.2018.12.022

DHHC4 and DHHC5 Facilitate Fatty Acid Uptake by Palmitoylating and Targeting CD36 to the Plasma Membrane

Juan Wang, Jian Wei Hao, Xu Wang, Huiling Guo, Hui Hui Sun, Xiao Ying Lai, Li Ying Liu, Mingxia Zhu, Hao Yan Wang, Yi Fan Li, Li Yang Yu, Changchuan Xie, Hong Rui Wang, Wei Mo, Hai Meng Zhou, Shuai Chen, Guosheng Liang, Tong Jin Zhao

Research output: Contribution to journal › Article › peer-review

99 Scopus citations

Abstract

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, both Dhhc4 ^−/− and adipose-specific Dhhc5 knockout 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.

Original language	English (US)
Pages (from-to)	209-221.e5
Journal	Cell Reports
Volume	26
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2018.12.022
State	Published - Jan 2 2019

Keywords

CD36
DHHC4
DHHC5
fatty acid uptake
protein palmitoylation

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2018.12.022

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Wang, J., Hao, J. W., Wang, X., Guo, H., Sun, H. H., Lai, X. Y., Liu, L. Y., Zhu, M., Wang, H. Y., Li, Y. F., Yu, L. Y., Xie, C., Wang, H. R., Mo, W., Zhou, H. M., Chen, S., Liang, G., & Zhao, T. J. (2019). DHHC4 and DHHC5 Facilitate Fatty Acid Uptake by Palmitoylating and Targeting CD36 to the Plasma Membrane. Cell Reports, 26(1), 209-221.e5. https://doi.org/10.1016/j.celrep.2018.12.022

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abstract = " 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, both Dhhc4 −/− and adipose-specific Dhhc5 knockout 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.",

keywords = "CD36, DHHC4, DHHC5, fatty acid uptake, protein palmitoylation",

author = "Juan Wang and Hao, {Jian Wei} and Xu Wang and Huiling Guo and Sun, {Hui Hui} and Lai, {Xiao Ying} and Liu, {Li Ying} and Mingxia Zhu and Wang, {Hao Yan} and Li, {Yi Fan} and Yu, {Li Yang} and Changchuan Xie and Wang, {Hong Rui} and Wei Mo and Zhou, {Hai Meng} and Shuai Chen and Guosheng Liang and Zhao, {Tong Jin}",

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AU - Hao, Jian Wei

AU - Wang, Xu

AU - Guo, Huiling

AU - Sun, Hui Hui

AU - Lai, Xiao Ying

AU - Liu, Li Ying

AU - Zhu, Mingxia

AU - Wang, Hao Yan

AU - Li, Yi Fan

AU - Yu, Li Yang

AU - Xie, Changchuan

AU - Wang, Hong Rui

AU - Mo, Wei

AU - Zhou, Hai Meng

AU - Chen, Shuai

AU - Liang, Guosheng

AU - Zhao, Tong Jin

PY - 2019/1/2

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N2 - 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, both Dhhc4 −/− and adipose-specific Dhhc5 knockout 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.

AB - 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, both Dhhc4 −/− and adipose-specific Dhhc5 knockout 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.

KW - CD36

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KW - DHHC5

KW - fatty acid uptake

KW - protein palmitoylation

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DHHC4 and DHHC5 Facilitate Fatty Acid Uptake by Palmitoylating and Targeting CD36 to the Plasma Membrane

Abstract

Keywords

ASJC Scopus subject areas

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