Open AccessSingle-cell metabolic imaging reveals a SLC2A3-dependent glycolytic burst in motile endothelial cells
Author(s) -
David Wu,
Devin Harrison,
Teodora Szasz,
ChihFan Yeh,
TzuPin Shentu,
Angelo Y. Meliton,
RuTing Huang,
Zhong Zhou,
Gökhan M. Mutlu,
Jun Huang,
Yun Fang
Publication year - 2021
Publication title -
nature metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.834
H-Index - 22
ISSN - 2522-5812
DOI - 10.1038/s42255-021-00390-y
Subject(s) - microbiology and biotechnology , motility , glycolysis , rhoa , biology , glut3 , endothelial stem cell , cytoskeleton , cell migration , focal adhesion , cell , biochemistry , signal transduction , glucose transporter , metabolism , glut1 , endocrinology , insulin , in vitro
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.