UMMS Affiliation

Program in Molecular Medicine; Department of Physiology

Publication Date


Document Type



Animals; COS Cells; Cell Membrane; Cercopithecus aethiops; Endosomes; Epidermal Growth Factor; Protein Transport; Signal Transduction; Transferrin; Vesicular Transport Proteins


Life Sciences | Medicine and Health Sciences


The biological function of receptors is determined by their appropriate trafficking through the endosomal pathway. Following internalization, the transferrin (Tf) receptor quantitatively recycles to the plasma membrane, whereas the epidermal growth factor (EGF) receptor undergoes degradation. To determine how Tf and EGF engage these two different pathways we imaged their binding and early endocytic pathway in live cells using total internal reflection fluorescence microscopy (TIRF-M). We find that EGF and Tf bind to distinct plasma membrane regions and are incorporated into different endocytic vesicles. After internalization, both EGF-enriched and Tf-enriched vesicles interact with endosomes containing early endosome antigen 1 (EEA1). EGF is incorporated and retained in these endosomes, while Tf-containing vesicles rapidly dissociate and move to a juxtanuclear compartment. Endocytic vesicles carrying EGF recruit more Rab5 GTPase than those carrying Tf, which, by strengthening their association with EEA1-enriched endosomes, may provide a mechanism for the observed cargo-specific sorting. These results reveal pre-endocytic sorting of Tf and EGF, a specialized role for EEA1-enriched endosomes in EGF trafficking, and a potential mechanism for cargo-specified sorting of endocytic vesicles by these endosomes.

DOI of Published Version



J Cell Sci. 2008 Oct 15;121(Pt 20):3445-58. Epub 2008 Sep 30. Link to article on publisher's site

Journal/Book/Conference Title

Journal of cell science

Related Resources

Link to Article in PubMed

PubMed ID