Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells

Howes, Mark T., Kirkham, Matthew, Riches, James, Cortese, Katia, Walser, Piers J., Simpson, Fiona, Hill, Michelle M., Jones, Alun, Lundmark, Richard, Lindsay, Margaret R., Hernandez-Deviez, Delia J., Hadzic, Gordana, McCluskey, Adam, Bashir, Rumasia, Liu, Libin, Pilch, Paul, McMahon, Harvey, Robinson, Phillip J., Hancock, John F., Mayor, Satyajit, & Parton, Robert G. (2010) Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells. The Journal of Cell Biology, 190(4), pp. 675-691.

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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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ID Code: 94941
Item Type: Journal Article
Refereed: Yes
DOI: 10.1083/jcb.201002119
ISSN: 1540-8140
Divisions: Current > Schools > School of Earth, Environmental & Biological Sciences
Current > Institutes > Institute for Future Environments
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Copyright Owner: 2010 Howes et al.
Copyright Statement: This article is distributed under the terms of an Attribution– Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at
Deposited On: 18 Apr 2016 22:40
Last Modified: 20 Apr 2016 03:27

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