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

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 intern...

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Bibliographic Details
Published in:	The Journal of cell biology Vol. 190; no. 4; pp. 675 - 691
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	United States The Rockefeller University Press 23-08-2010 Rockefeller University Press
Subjects:	Animals Antibodies Biological Transport - physiology Biomarkers - metabolism Caveolae Caveolin 1 - genetics Caveolin 1 - metabolism Cell adhesion & migration Cell Membrane - metabolism Cell Membrane - ultrastructure Cell membranes Cell Movement - physiology Cell Polarity Cells Clathrin - metabolism Endocytosis Endocytosis - physiology Endosomes - metabolism Endosomes - ultrastructure Fibroblasts Fibroblasts - metabolism Fibroblasts - ultrastructure Freight Ice Internalization Membranes Mice Mice, Knockout NIH 3T3 Cells P branes Proteins Proteomics Subcellular Fractions - chemistry Subcellular Fractions - metabolism
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 K. Cortese’s present address is Centro di Ricerca MicroSCoBio/IFOM, FIRC Institute of Molecular Oncology, Università di Genova, 16126 Genova, Italy. F. Simpson’s and M.M. Hill’s present address is The University of Queensland, Diamentina Institute for Cancer, Immunology and Metabolic Medicine, Brisbane, Queeensland 4102, Australia. M. Kirkham’s present address is Department of Cell and Molecular Biology, Karolinska Institute, 17177 Stockholm, Sweden. J. Riches’ present address is European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. R. Lundmark’s present address is Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
ISSN:	0021-9525 1540-8140 1540-8140
DOI:	10.1083/jcb.201002119