Abstract:
:Endosomal trafficking of signaling proteins plays an essential role in cellular homeostasis. The seven-pass transmembrane protein Frizzled (Fz) is a critical component of Wnt signaling. Although Wnt signaling is proposed to be regulated by endosomal trafficking of Fz, the molecular events that enable this regulation are not completely understood. Here we show that the endosomal protein Myopic (Mop) regulates Fz trafficking in the Drosophila wing disk by inhibiting the ubiquitination and degradation of Hrs. Deletion of Mop or Hrs results in endosomal accumulation of Fz and therefore reduced Wnt signaling. The in situ proximity ligation assay revealed a strong association between Mop and Hrs in the Drosophila wing disk. Overexpression of Hrs rescues the trafficking defect caused by mop knockdown. Mop aids in the maintenance of Ubpy, which deubiquitinates (and thus stabilizes) Hrs. In the absence of the ubiquitin ligase Cbl, Mop is dispensable. These findings support a previously unknown role for Mop in endosomal trafficking of Fz in Wnt-receiving cells.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Pradhan-Sundd T,Verheyen EMdoi
10.1091/mbc.E15-02-0086subject
Has Abstractpub_date
2015-09-15 00:00:00pages
3329-42issue
18eissn
1059-1524issn
1939-4586pii
mbc.E15-02-0086journal_volume
26pub_type
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