A novel endocytic mechanism of epidermal growth factor receptor sequestration and internalization

James D. Orth, Eugene W. Krueger, Shaun G. Weller, Mark A. McNiven

Research output: Contribution to journalArticlepeer-review

171 Scopus citations

Abstract

Cells form transient, circular dorsal ruffles or "waves" in response to stimulation of receptor tyrosine kinases, including epidermal growth factor receptor (EGFR) or platelet-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 ~ 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.

Original languageEnglish (US)
Pages (from-to)3603-3610
Number of pages8
JournalCancer research
Volume66
Issue number7
DOIs
StatePublished - Apr 1 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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