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

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posted on 2025-05-09, 07:10 authored by Mark T. Howes, Matthew Kirkham, Delia J. Hernandez-Deviez, Gordana Hadzic, Adam McCluskeyAdam McCluskey, Rumasia Bashir, Libin Liu, Paul Pilch, Harvey McMahon, Phillip J. Robinson, John F. Hancock, Satyajit Mayor, James Riches, Robert G. Parton, Katia Cortese, Piers J. Walser, Fiona Simpson, Michelle M. Hill, Alun Jones, Richard Lundmark, Margaret R. Lindsay
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.

History

Journal title

Journal of Cell Biology

Volume

190

Issue

4

Pagination

675-691

Publisher

Rockefeller University Press

Language

  • en, English

College/Research Centre

Faculty of Science and Information Technology

School

School of Environmental and Life Sciences

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