Quantification of lipid sorting during clathrin-mediated endocytosis

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Contributors

  • H. Mathilda Lennartz - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Susana da Costa Nunes - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Kristin Böhlig - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Aditya Chhatre - , Chair of Biophysics (Author)
  • Radek Šachl - , Czech Academy of Sciences (Author)
  • Sascha M. Kuhn - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Lior Moneta - , Max Planck Institute of Molecular Cell Biology and Genetics, Center for Systems Biology Dresden (CSBD) (Author)
  • Pavel Barahtjan - , Max Planck Institute of Molecular Cell Biology and Genetics, Swiss Federal Institute of Technology Lausanne (EPFL) (Author)
  • Wan Yee Yau - , Max Planck Institute of Molecular Cell Biology and Genetics, Center for Systems Biology Dresden (CSBD) (Author)
  • Juan M. Iglesias-Artola - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Martin Hof - , Czech Academy of Sciences (Author)
  • Lukáš Opálka - , Charles University Prague (Author)
  • Carl D. Modes - , Max Planck Institute of Molecular Cell Biology and Genetics, Center for Systems Biology Dresden (CSBD), Clusters of Excellence PoL: Physics of Life (Author)
  • Alf Honigmann - , Clusters of Excellence PoL: Physics of Life, Chair of Biophysics (Author)
  • André Nadler - , Max Planck Institute of Molecular Cell Biology and Genetics, Clusters of Excellence PoL: Physics of Life (Author)

Abstract

Clathrin-mediated endocytosis is a major transport route for proteins from the plasma membrane to the interior of the cell. While the recruitment of cargo proteins to clathrin-coated pits is well understood, it remains an open question whether lipids are also sorted by this process. Here, to address this question, we combined super-resolution stimulated emission depletion imaging of bifunctional lipid probes with mathematical modelling. Quantification of ten different lipid species revealed significant differences in pit partitioning, ranging from slight enrichment to moderate exclusion. We find that the lipid asymmetry in the plasma membrane is sufficient to explain the observed trend. Taken together, our findings imply that clathrin-mediated endocytosis has a minor selectivity for cytoplasmic leaflet lipids, but overall does not substantially contribute to lipid sorting compared with non-vesicular trafficking.

Details

Original languageEnglish
JournalNature cell biology
Publication statusE-pub ahead of print - 29 Sept 2026
Peer-reviewedYes

External IDs

ORCID /0000-0003-0475-3790/work/229893699

Keywords

ASJC Scopus subject areas