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CD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis

Author

Listed:
  • Jian-Wei Hao

    (Xiamen University)

  • Juan Wang

    (Xiamen University
    Fudan University)

  • Huiling Guo

    (Xiamen University)

  • Yin-Yue Zhao

    (Xiamen University)

  • Hui-Hui Sun

    (Xiamen University)

  • Yi-Fan Li

    (Xiamen University)

  • Xiao-Ying Lai

    (Xiamen University)

  • Ning Zhao

    (Xiamen University)

  • Xu Wang

    (Fudan University)

  • Changchuan Xie

    (Xiamen University)

  • Lixin Hong

    (Xiamen University)

  • Xi Huang

    (Xiamen University)

  • Hong-Rui Wang

    (Xiamen University
    Xiamen University)

  • Cheng-Bin Li

    (Yunnan University)

  • Bin Liang

    (Yunnan University)

  • Shuai Chen

    (Nanjing University)

  • Tong-Jin Zhao

    (Xiamen University
    Fudan University
    Xiamen University)

Abstract

Fatty acids (FAs) are essential nutrients, but how they are transported into cells remains unclear. Here, we show that FAs trigger caveolae-dependent CD36 internalization, which in turn delivers FAs into adipocytes. During the process, binding of FAs to CD36 activates its downstream kinase LYN, which phosphorylates DHHC5, the palmitoyl acyltransferase of CD36, at Tyr91 and inactivates it. CD36 then gets depalmitoylated by APT1 and recruits another tyrosine kinase SYK to phosphorylate JNK and VAVs to initiate endocytic uptake of FAs. Blocking CD36 internalization by inhibiting APT1, LYN or SYK abolishes CD36-dependent FA uptake. Restricting CD36 at either palmitoylated or depalmitoylated state eliminates its FA uptake activity, indicating an essential role of dynamic palmitoylation of CD36. Furthermore, blocking endocytosis by targeting LYN or SYK inhibits CD36-dependent lipid droplet growth in adipocytes and high-fat-diet induced weight gain in mice. Our study has uncovered a dynamic palmitoylation-regulated endocytic pathway to take up FAs.

Suggested Citation

  • Jian-Wei Hao & Juan Wang & Huiling Guo & Yin-Yue Zhao & Hui-Hui Sun & Yi-Fan Li & Xiao-Ying Lai & Ning Zhao & Xu Wang & Changchuan Xie & Lixin Hong & Xi Huang & Hong-Rui Wang & Cheng-Bin Li & Bin Lian, 2020. "CD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18565-8
    DOI: 10.1038/s41467-020-18565-8
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    Cited by:

    1. Phillip M. Brailey & Lauren Evans & Juan Carlos López-Rodríguez & Anthony Sinadinos & Victoria Tyrrel & Gavin Kelly & Valerie O’Donnell & Peter Ghazal & Susan John & Patricia Barral, 2022. "CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Graham A. Heieis & Thiago A. Patente & Luís Almeida & Frank Vrieling & Tamar Tak & Georgia Perona-Wright & Rick M. Maizels & Rinke Stienstra & Bart Everts, 2023. "Metabolic heterogeneity of tissue-resident macrophages in homeostasis and during helminth infection," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. V. S. Peche & T. A. Pietka & M. Jacome-Sosa & D. Samovski & H. Palacios & G. Chatterjee-Basu & A. C. Dudley & W. Beatty & G. A. Meyer & I. J. Goldberg & N. A. Abumrad, 2023. "Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Shao-Chin Wu & Yuan-Ming Lo & Jui-Hao Lee & Chin-Yau Chen & Tung-Wei Chen & Hong-Wen Liu & Wei-Nan Lian & Kate Hua & Chen-Chung Liao & Wei-Ju Lin & Chih-Yung Yang & Chien-Yi Tung & Chi-Hung Lin, 2022. "Stomatin modulates adipogenesis through the ERK pathway and regulates fatty acid uptake and lipid droplet growth," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Li Weng & Wen-Shuai Tang & Xu Wang & Yingyun Gong & Changqin Liu & Ni-Na Hong & Ying Tao & Kuang-Zheng Li & Shu-Ning Liu & Wanzi Jiang & Ying Li & Ke Yao & Li Chen & He Huang & Yu-Zheng Zhao & Ze-Ping, 2024. "Surplus fatty acid synthesis increases oxidative stress in adipocytes and induces lipodystrophy," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    6. Yanjie Tan & Zhenzhou Huang & Yi Jin & Jiaying Wang & Hongjun Fan & Yangyang Liu & Liang Zhang & Yue Wu & Peiwei Liu & Tianliang Li & Jie Ran & He Tian & Sin Man Lam & Min Liu & Jun Zhou & Yunfan Yang, 2024. "Lipid droplets sequester palmitic acid to disrupt endothelial ciliation and exacerbate atherosclerosis in male mice," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    7. Jian Xiao & Le-Wei Dong & Shuai Liu & Fan-Hua Meng & Chang Xie & Xiao-Yi Lu & Weiping J. Zhang & Jie Luo & Bao-Liang Song, 2023. "Bile acids-mediated intracellular cholesterol transport promotes intestinal cholesterol absorption and NPC1L1 recycling," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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