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A role for Hrs in endosomal sorting of ligand-stimulated and unstimulated epidermal growth factor receptor
Abstract
Ligand-stimulated growth factor receptors are rapidly internalized and transported to early endosomes. Unstimulated receptors are also internalized constitutively, although at a slower rate, and delivered to the same organelle. At early endosomes, stimulated receptors are sorted for the lysosomal degradation pathway, whereas unstimulated receptors are mostly recycled back to the cell surface. To investigate the role of Hrs, an early endosomal protein, in this sorting process, we overexpressed Hrs in HeLa cells and examined the intracellular trafficking of epidermal growth factor receptor (EGFR) in EGF-stimulated and unstimulated cells. Overexpression of Hrs inhibited the trafficking of EGFR from early endosomes, resulting in an accumulation of EGFR on early endosomes in both ligand-stimulated and unstimulated cells. On the other hand, overexpression of Hrs mutants with a deletion or a point mutation within the FYVE domain did not inhibit the trafficking. These results suggest that Hrs regulates the sorting of ligand-stimulated and unstimulated growth factor receptors on early endosomes, and that the FYVE domain, which is required for Hrs to reside in a microdomain of early endosomes, plays an essential role in the function of Hrs.
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STAM-mediated recruitment of USP8 for deubiquitination at the ESCRT-0 complex may curtail EGFR sorting into late endosomal compartments.
“As Hrs and STAM comprise the ESCRT-0 complex implicated in the early steps of receptor trafficking (18,50), our observations, therefore, imply that STAM-mediated recruitment of USP8 for deubiquitination at this juncture may curtail EGFR sorting into the late endosomal compartments.”
From Regulation of Epidermal Growth Factor Receptor Ubiquitination and Trafficking by the USP8·STAM Complex (2010) · cites this paper as [50]
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Sorted by citations
Berlin, I., Schwartz, H., & Nash, P. D. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.016287 · Cited by 121
Metadata
- Authors
- Morino, C., Kato, M., Yamamoto, A., Mizuno, E., Hayakawa, A., Komada, M., & Kitamura, N.
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 297
- Issue
- 2
- Pages
- 380-391
- ISSN
- 0014-4827
- Cited by
- 33
- References
- 2
- Language
- en
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (15370053)
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