Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells
Open accessAbstract
Although the importance of clathrin- and caveolin-independent endocytic pathways has recently emerged, key aspects of these routes remain unknown. Using quantitative ultrastructural approaches, we show that clathrin-independent carriers (CLICs) account for approximately three times the volume internalized by the clathrin-mediated endocytic pathway, forming the major pathway involved in uptake of fluid and bulk membrane in fibroblasts. Electron tomographic analysis of the 3D morphology of the earliest carriers shows that they are multidomain organelles that form a complex sorting station as they mature. Proteomic analysis provides direct links between CLICs, cellular adhesion turnover, and migration. Consistent with this, CLIC-mediated endocytosis of key cargo proteins, CD44 and Thy-1, is polarized at the leading edge of migrating fibroblasts, while transient ablation of CLICs impairs their ability to migrate. These studies provide the first quantitative ultrastructural analysis and molecular characterization of the major endocytic pathway in fibroblasts, a pathway that provides rapid membrane turnover at the leading edge of migrating cells.
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Receptor-mediated endocytosis is further classified into clathrin-mediated endocytosis, caveolin-mediated endocytosis, caveolin-independent endocytosis, and clathrin-independent endocytosis.
“The receptor-mediated endocytosis has been further classified into several subtypes, such as clathrin-mediated endocytosis (CME), Caveolin-mediated endocytosis (CavME), Caveolin-independent endocytosis (CavIE), and Clathrin-independent endocytosis (CIE) [6,7,8,9].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [8]
The Introduction (p. 1) distinguishes clathrin-mediated endocytosis, caveolae, and noncaveolar clathrin-independent routes. It describes these as constitutive pinocytic pathways, not specifically as subtypes of receptor-mediated endocytosis, and does not present caveolin-independent and clathrin-independent endocytosis as separate categories. (LLM, conf=0.86)
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“This binding promotes the biogenesis of tubular endocytic pits [8,9].”
Background
- Authors
- Howes, M. T., Kirkham, M., Riches, J., Cortese, K., Walser, P. J., Simpson, F., Hill, M. M., Jones, A., Lundmark, R., Lindsay, M. R., Hernandez-Deviez, D. J., Hadzic, G., McCluskey, A., Bashir, R., Liu, L., Pilch, P., McMahon, H., Robinson, P. J., Hancock, J. F., Mayor, S., & Parton, R. G.
- Affiliations
- The University of Queensland (AU)
- MRC Laboratory of Molecular Biology (GB)
- The Institute for Molecular Bioscience 1 and 2
- University of Newcastle Australia (AU)
- Durham University (GB)
- Boston University (US)
- The University of Sydney (AU)
- National Centre for Biological Sciences (IN)
- Corresponding author
- Parton, Robert G.
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2010-08-16
- Volume
- 190
- Issue
- 4
- Pages
- 675-691
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2928008
- OpenAlex
- W2151888693
- Cited by
- 303
- References
- 59
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 8 · 2023: 12 · 2022: 11 · 2021: 21 · 2020: 24 · 2019: 17 · 2018: 20 · 2017: 17 · 2016: 12 · 2015: 40 · 2014: 26 · 2013: 28 · 2012: 25
- FWCI
- 10.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Durham Research Online (Durham University) (acceptedVersion, cc-by-nc-sa)
- Durham Research Online (Durham University) (submittedVersion, cc-by-nc-sa)
- Figshare (submittedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Institute for Future Environments; Science & Engineering Faculty
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- endocytic sorting, cell migration, leading edge, fibroblasts, membrane turnover, CD44, CD90, membrane internalization, electron tomography, ultrastructure
- MeSH terms
- Animals, Biological Transport, Cell Membrane, Cell Movement, Clathrin, Endocytosis, Fibroblasts, Endosomes, Subcellular Fractions, Biomarkers, Cell Polarity, Mice, Knockout, NIH 3T3 Cells, Caveolin 1, Mice
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