Single-cell metabolic imaging reveals a SLC2A3-dependent glycolytic burst in motile endothelial cells

Single-cell motility is spatially heterogeneous and driven by metabolic energy. Directly linking cell motility to cell metabolism is technically challenging but biologically important. Here, we use single-cell metabolic imaging to measure glycolysis in individual endothelial cells with genetically e...

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Bibliographic Details
Published inNature metabolism Vol. 3; no. 5; p. 714
Main Authors Wu, David, Harrison, Devin L, Szasz, Teodora, Yeh, Chih-Fan, Shentu, Tzu-Pin, Meliton, Angelo, Huang, Ru-Ting, Zhou, Zhengjie, Mutlu, Gökhan M, Huang, Jun, Fang, Yun
Format Journal Article
LanguageEnglish
Published Germany 01.05.2021
Subjects
Biomarkers
Cell Movement
Cells, Cultured
Computational Biology - methods
Cytoskeleton - metabolism
Endothelial Cells - metabolism
Endothelium, Vascular
Energy Metabolism
Glucose - metabolism
Glucose Transporter Type 3 - genetics
Glucose Transporter Type 3 - metabolism
Glycolysis
Humans
Mechanical Phenomena
Models, Biological
Molecular Imaging - methods
rhoA GTP-Binding Protein - metabolism
Single-Cell Analysis - methods
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Summary:Single-cell motility is spatially heterogeneous and driven by metabolic energy. Directly linking cell motility to cell metabolism is technically challenging but biologically important. Here, we use single-cell metabolic imaging to measure glycolysis in individual endothelial cells with genetically encoded biosensors capable of deciphering metabolic heterogeneity at subcellular resolution. We show that cellular glycolysis fuels endothelial activation, migration and contraction and that sites of high lactate production colocalize with active cytoskeletal remodelling within an endothelial cell. Mechanistically, RhoA induces endothelial glycolysis for the phosphorylation of cofilin and myosin light chain in order to reorganize the cytoskeleton and thus control cell motility; RhoA activation triggers a glycolytic burst through the translocation of the glucose transporter SLC2A3/GLUT3 to fuel the cellular contractile machinery, as demonstrated across multiple endothelial cell types. Our data indicate that Rho-GTPase signalling coordinates energy metabolism with cytoskeleton remodelling to regulate endothelial cell motility.
ISSN:2522-5812
DOI:10.1038/s42255-021-00390-y