Flotillin-1 defines a clathrin-independent endocytic pathway in mammalian cells

被引:438
作者
Glebov, OO
Bright, NA
Nichols, BJ
机构
[1] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
[2] Cambridge Inst Med Res, Cambridge CB2 2XY, England
基金
英国医学研究理事会;
关键词
D O I
10.1038/ncb1342
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Previous studies provide evidence for an endocytic mechanism in mammalian cells that is distinct from both clathrin- coated pits and caveolae(1-5), and is not inhibited by overexpression of GTPase- null dynamin mutants(1-4,6). 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 glycosyl phosphatidylinositol ( GPI)- linked proteins and cholera toxin B subunit(4,9). 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 caveolae(10). 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.
引用
收藏
页码:46 / U16
页数:12
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