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Hrs mediates downregulation of multiple signalling receptors in Drosophila
Author(s) -
Jékely Gáspár,
Rørth Pernille
Publication year - 2003
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400019
Subject(s) - microbiology and biotechnology , receptor , endocytosis , receptor tyrosine kinase , endosome , ubiquitin , biology , downregulation and upregulation , signalling , hedgehog , hedgehog signaling pathway , signal transduction , receptor protein tyrosine kinases , biochemistry , gene
Endocytosis and subsequent lysosomal degradation of activated signalling receptors can attenuate signalling. Endocytosis may also promote signalling by targeting receptors to specific compartments. A key step regulating the degradation of receptors is their ubiquitination. Hrs/Vps27p, an endosome‐associated, ubiquitin‐binding protein, affects sorting and degradation of receptors. Drosophila embryos mutant for hrs show elevated receptor tyrosine kinase (RTK) signalling. Hrs has also been proposed to act as a positive mediator of TGF‐β signalling. We find that Drosophila epithelial cells devoid of Hrs accumulate multiple signalling receptors in an endosomal compartment with high levels of ubiquitinated proteins: not only RTKs (EGFR and PVR) but also Notch and receptors for Hedgehog and Dpp (TGF‐β related). Hrs is not required for Dpp signalling. Instead, loss of Hrs increases Dpp signalling and the level of the type‐I receptor Thickveins (Tkv). Finally, most hrs ‐dependent receptor turnover appears to be ligand independent. Thus, both active and inactive signalling receptors are targeted for degradation in vivo and Hrs is required for their removal.