Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila

Thomas Lloyd, Richard Atkinson, Mark Wu, Yi Zhou, Giuseppa Pennetta, Hugo J. Bellen

Research output: Contribution to journalArticle

Abstract

Signaling through tyrosine kinase receptors (TKRs) is thought to be modulated by receptor-mediated endocytosis and degradation of the receptor in the lysosome. However, factors that regulate endosomal sorting of TKRs are largely unknown. Here, we demonstrate that Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) is one such factor. Electron microscopy studies of hrs mutant larvae reveal an impairment in endosome membrane invagination and formation of multivesicular bodies (MVBs). hrs mutant animals fail to degrade active epidermal growth factor (EGF) and Torso TKRs, leading to enhanced signaling and altered embryonic patterning. These data suggest that Hrs and MVB formation function to downregulate TKR signaling.

Original languageEnglish (US)
Pages (from-to)261-269
Number of pages9
JournalCell
Volume108
Issue number2
DOIs
StatePublished - Jan 25 2002
Externally publishedYes

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Endosomes
Receptor Protein-Tyrosine Kinases
Drosophila
Multivesicular Bodies
Membranes
Torso
Endocytosis
Lysosomes
Sorting
Epidermal Growth Factor
Electron microscopy
Larva
Electron Microscopy
Animals
Down-Regulation
Degradation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila. / Lloyd, Thomas; Atkinson, Richard; Wu, Mark; Zhou, Yi; Pennetta, Giuseppa; Bellen, Hugo J.

In: Cell, Vol. 108, No. 2, 25.01.2002, p. 261-269.

Research output: Contribution to journalArticle

Lloyd, Thomas ; Atkinson, Richard ; Wu, Mark ; Zhou, Yi ; Pennetta, Giuseppa ; Bellen, Hugo J. / Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila. In: Cell. 2002 ; Vol. 108, No. 2. pp. 261-269.
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