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

Howes, M.T. and Kirkham, M. and Riches, J. and Cortese, K. and Walser, P.J. and Simpson, F. and Hill, M.M. and Jones, A. and Lundmark, R. and Lindsay, M.R. and Hernandez-Deviez, D.J. and Hadzic, G. and McCluskey, A. and Bashir, R. and Liu, L. and Pilch, P. and McMahon, H. and Robinson, P.J. and Hancock, J.F. and Mayor, S. and Parton, R.G (2010) 'Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells.', Journal of cell biology., 190 (4). pp. 675-691.


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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Publisher statement:© 2010 Howes et al. 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
Record Created:04 Jun 2012 16:50
Last Modified:12 Jun 2012 11:04

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