First Author | Mössinger J | Year | 2012 |
Journal | EMBO Rep | Volume | 13 |
Issue | 12 | Pages | 1087-94 |
PubMed ID | 23146885 | Mgi Jnum | J:200471 |
Mgi Id | MGI:5508700 | Doi | 10.1038/embor.2012.164 |
Citation | Mossinger J, et al. (2012) Phosphatidylinositol 4-kinase IIalpha function at endosomes is regulated by the ubiquitin ligase Itch. EMBO Rep 13(12):1087-94 |
abstractText | Phosphatidylinositol (PI) 4-phosphate (PI(4)P) and its metabolizing enzymes serve important functions in cell signalling and membrane traffic. PI 4-kinase type IIalpha (PI4KIIalpha) regulates Wnt signalling, endosomal sorting of signalling receptors, and promotes adaptor protein recruitment to endosomes and the trans-Golgi network. Here we identify the E3 ubiquitin ligase Itch as binding partner and regulator of PI4KIIalpha function. Itch directly associates with and ubiquitinates PI4KIIalpha, and both proteins colocalize on endosomes containing Wnt-activated frizzled 4 (Fz4) receptor. Depletion of PI4KIIalpha or Itch regulates Wnt signalling with corresponding changes in Fz4 internalization and degradative sorting. These findings unravel a new molecular link between phosphoinositide-regulated endosomal membrane traffic, ubiquitin and the modulation of Wnt signalling. |