Quantification of lipid sorting during clathrin-mediated endocytosis
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.
Authors
- Kristin Böhlig (ORCID: https://orcid.org/0000-0002-8286-1992)
- Martin Hof (ORCID: https://orcid.org/0000-0003-2884-3037)
- Carl D. Modes (ORCID: https://orcid.org/0000-0001-9940-0730)
- Lukáš Opálka (ORCID: https://orcid.org/0000-0003-1379-1406)
- Sascha M. Kuhn (ORCID: https://orcid.org/0000-0001-5009-1121)
- Juan Manuel Iglesias‐Artola (ORCID: https://orcid.org/0000-0002-0409-795X)
- Wan Yee Yau (ORCID: https://orcid.org/0009-0006-9623-7281)
- H. Mathilda Lennartz (ORCID: https://orcid.org/0000-0003-1159-613X)
- Alf Honigmann (ORCID: https://orcid.org/0000-0003-0475-3790)
- Aditya Chhatre (ORCID: https://orcid.org/0000-0001-8434-4502)
- Pavel Barahtjan (ORCID: https://orcid.org/0000-0003-0670-5717)
- Susana da Costa Nunes (ORCID: https://orcid.org/0009-0009-8759-9768)
- Radek Šachl (ORCID: https://orcid.org/0000-0002-0441-3908)
- André Nadler (ORCID: https://orcid.org/0000-0001-6329-3910)
- Lior Moneta (ORCID: https://orcid.org/0009-0009-9883-7696)
Institutions
- Czech Academy of Sciences (CZ)
- Charles University (CZ)
- Czech Academy of Sciences, J. Heyrovský Institute of Physical Chemistry (CZ)
- Center for Systems Biology Dresden (DE)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- Physics of Life (DE)
- École Polytechnique Fédérale de Lausanne (CH)
- Technische Universität Dresden (DE)
Publication Details
- Journal
- Nature Cell Biology
- Published
- 2026-09-29
- DOI
- https://doi.org/10.1038/s41556-026-02068-7
- Primary Topic
- Cellular transport and secretion
- Type
- article
- Field-Weighted Citation Impact
- 0.00