Letter abstract
Nature Cell Biology 8, 46 - 54 (2006)
Published online: 11 December 2005 | doi:10.1038/ncb1342
Flotillin-1 defines a clathrin-independent endocytic pathway in mammalian cells
Oleg O. Glebov1, Nicholas A. Bright2 & Benjamin J. Nichols1
Previous studies provide evidence for an endocytic mechanism in mammalian cells that is distinct from both clathrin-coated pits and caveolae1, 2, 3, 4, 5, and is not inhibited by overexpression of GTPase-null dynamin mutants1, 2, 3, 4, 6. This mechanism, however, has been defined largely in these negative terms. We applied a ferro-fluid-based purification of endosomes to identify endosomal proteins. One of the proteins identified in this way was flotillin-1 (also called reggie-2)7, 8. Here, we show that flotillin-1 resides in punctate structures within the plasma membrane and in a specific population of endocytic intermediates. These intermediates accumulate both glycosylphosphatidylinositol (GPI)-linked proteins and cholera toxin B subunit4, 9. Endocytosis in flotillin-1-containing intermediates is clathrin-independent. Total internal reflection microscopy and immuno-electron microscopy revealed that flotillin-1-containing regions of the plasma membrane seem to bud into the cell, and are distinct from clathrin-coated pits and caveolin-1-positive caveolae10. Flotillin-1 small interfering RNA (siRNA) inhibited both clathrin-independent uptake of cholera toxin and endocytosis of a GPI-linked protein. We propose that flotillin-1 is one determinant of a clathrin-independent endocytic pathway in mammalian cells.
- MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
- Cambridge Institute of Medical Research, Hills Road, Cambridge CB2 2XY, UK.
Correspondence to: Benjamin J. Nichols1 e-mail: ben@mrc-lmb.cam.ac.uk
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