| First Author | Schmid FM | Year | 2018 |
| Journal | J Cell Biol | Volume | 217 |
| Issue | 1 | Pages | 151-161 |
| PubMed ID | 29237719 | Mgi Jnum | J:281256 |
| Mgi Id | MGI:6108066 | Doi | 10.1083/jcb.201611050 |
| Citation | Schmid FM, et al. (2018) IFT20 modulates ciliary PDGFRalpha signaling by regulating the stability of Cbl E3 ubiquitin ligases. J Cell Biol 217(1):151-161 |
| abstractText | Primary cilia have pivotal roles as organizers of many different signaling pathways, including platelet-derived growth factor receptor alpha (PDGFRalpha) signaling, which, when aberrantly regulated, is associated with developmental disorders, tumorigenesis, and cancer. PDGFRalpha is up-regulated during ciliogenesis, and ciliary localization of the receptor is required for its appropriate ligand-mediated activation by PDGF-AA. However, the mechanisms regulating sorting of PDGFRalpha and feedback inhibition of PDGFRalpha signaling at the cilium are unknown. Here, we provide evidence that intraflagellar transport protein 20 (IFT20) interacts with E3 ubiquitin ligases c-Cbl and Cbl-b and is required for Cbl-mediated ubiquitination and internalization of PDGFRalpha for feedback inhibition of receptor signaling. In wild-type cells treated with PDGF-AA, c-Cbl becomes enriched in the cilium, and the receptor is subsequently ubiquitinated and internalized. In contrast, in IFT20-depleted cells, PDGFRalpha localizes aberrantly to the plasma membrane and is overactivated after ligand stimulation because of destabilization and degradation of c-Cbl and Cbl-b. |
