2. Academic Validation
  3. 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

  • Cell Rep. 2019 Jan 2;26(1):209-221.e5. doi: 10.1016/j.celrep.2018.12.022.
Juan Wang 1,  Jian-Wei Hao 1,  Xu Wang 1,  Huiling Guo 1,  Hui-Hui Sun 1,  Xiao-Ying Lai 1,  Li-Ying Liu 1,  Mingxia Zhu 1,  Hao-Yan Wang 1,  Yi-Fan Li 1,  Li-Yang Yu 1,  Changchuan Xie 1,  Hong-Rui Wang 1,  Wei Mo 1,  Hai-Meng Zhou 2,  Shuai Chen 3,  Guosheng Liang 4,  Tong-Jin Zhao 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China, 361102.
  • 2 Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing, Zhejiang, China, 314006.
  • 3 MOE Key Laboratory of Model Animal for Disease Study and State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Pukou District, Nanjing, China, 210061.
  • 4 Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 5 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China, 361102. Electronic address: [email protected].
PMID: 30605677 DOI: 10.1016/j.celrep.2018.12.022
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.

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