A novel endocytic mechanism of epidermal growth factor receptor sequestration and internalization
A novel endocytic mechanism of epidermal growth factor receptor sequestration and internalization
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DOI：
10.1158/0008-5472.can-05-2916
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发表时间：
2006-04-01
期刊：
影响因子：
11.2
通讯作者：
McNiven, MA
中科院分区：
文献类型：
--
作者：
Orth, JD;Krueger, EW;McNiven, MA
Cells form transient, circular dorsal ruffles or "waves" in response to stimulation of receptor tyrosine kinases, including epidermal growth factor receptor (EGFR) or plate] et-derived growth factor receptor. These dynamic structures progress inward on the dorsal surface and disappear, occurring concomitantly with a marked reorganization of F-actin. The cellular function of these structures is largely unknown. Here we show that EGF-induced waves selectively sequester and internalize similar to 50% of ligand-bound EGFR from the cell surface. This process requires receptor phosphorylation, active phosphatidylinositol 3-kinase, and dynamin 2, although clathrin- coated pits or caveolae are not required. Epithelial and fibroblast cells stimulated with EGF sequestered EGFR rapidly into waves that subsequently generated numerous receptor-positive tubular-vesicular structures. Electron microscopy confirmed that waves formed along the dorsal membrane surface and extended numerous tubules into the cytoplasm. These findings characterize a structure that selectively sequesters large numbers of activated EGFR for their subsequent internalization, independent of traditional endocytic mechanisms such as clathrin pits or caveolae.
