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Cited by 423Lipid metabolism and biosynthesisCaveolin-1 and cellular processesCancer, Lipids, and Metabolism

CD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis

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Hao, Jian-Wei, Wang, Juan, Guo, Huiling, Zhao, Yin-Yue, Sun, Hui-Hui, Li, Yi-Fan, Lai, Xiao-Ying, Zhao, Ning +9 more·2020·Nature Communications
DOI 10.1038/s41467-020-18565-8PMC PMC7505845
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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.

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  • FA uptake mediated by CD36 is a palmitoylation-regulated endocytic pathway.

    “Additionally, the FA uptake mediated by CD36 is a palmitoylation-regulated endocytic pathway [140].”

    From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [140]

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Authors
Hao, J.-W., Wang, J., Guo, H., Zhao, Y.-Y., Sun, H.-H., Li, Y.-F., Lai, X.-Y., Zhao, N., Wang, X., Xie, C., Hong, L., Huang, X., Wang, H.-R., Li, C.-B., Liang, B., Chen, S., & Zhao, T.-J.
Affiliations
  • Xiamen University (CN)
  • Fudan University (CN)
  • Yunnan University (CN)
  • Model Animal Research Center (CN)
Corresponding author
  • Chen, Shuai
  • Zhao, Tong-Jin
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2020-09-21
Volume
11
Issue
1
Pages
4765-4765
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-020-18565-8
PMC
PMC7505845
OpenAlex
W3087320494
Cited by
423
References
0
Citations by year
2026: 65 · 2025: 102 · 2024: 94 · 2023: 69 · 2022: 55 · 2021: 36 · 2020: 2
FWCI
17.34
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81772818, 31671223)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
CD36, fatty acid uptake, palmitoylation, endocytosis, caveolae, adipocytes, Lyn kinase, APT1, Syk, JNK, Vav, lipid droplet growth, high-fat diet, weight gain, membrane protein internalization
MeSH terms
Syk Kinase, Acyltransferases, Animals, Cells, Cultured, Endocytosis, Fatty Acids, Humans, Male, Membrane Proteins, Mice, Inbred C57BL, Mutation, Obesity, Phosphorylation, Signal Transduction, Weight Gain, Adipocytes, Mice, Knockout, CD36 Antigens, src-Family Kinases, Caveolae, 3T3-L1 Cells, Mice, Lipoylation, Diet, High-Fat, Lipid Droplets

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