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PMID: 18827013 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Sorting of EGF and transferrin at the plasma membrane and by cargo-specific signaling to EEA1-enriched endosomes.

Journal of cell science ·Vol. 121 ·No. Pt 20 ·2008-10-15 ·Pages 3445-58

Leonard D, Hayakawa A, Lawe D, Lambright D, Bellve KD, Standley C, Lifshitz LM, Fogarty KE, Corvera S

Abstract

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.

MeSH Terms
Animals COS Cells Cell Membrane/metabolism Chlorocebus aethiops Endosomes/metabolism Epidermal Growth Factor/metabolism Protein Transport/physiology Signal Transduction/physiology Transferrin/metabolism Vesicular Transport Proteins/metabolism
Chemicals
Transferrin Vesicular Transport Proteins early endosome antigen 1 Epidermal Growth Factor
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Leonard Deborah
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Hayakawa Akira
Lawe Deirdre
Lambright David
Bellve Karl D
Standley Clive
Lifshitz Lawrence M
Fogarty Kevin E
Corvera Silvia
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Article Info
Journal
Journal of cell science
Abbr.
J Cell Sci
ISSN
0021-9533
DOI
10.1242/jcs.031484
Published
2008-10-15
Epub
2008-00-30
Pages
3445-58
Language
English
Region
England
NLM ID
0052457
PMCID
PMC2586290
Subset
IM
Grants
NIDDK NIH HHS · P01 DK060564-070002 · United States
NIDDK NIH HHS · P30 DK032520 · United States
NIDDK NIH HHS · DK32520 · United States
NIDDK NIH HHS · P01 DK060564 · United States
NIDDK NIH HHS · P01 DK60564 · United States
External Links
PubMed source DOI: 10.1242/jcs.031484 PMC Full Text View journal details
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