| First Author | Fansa EK | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 11366 | PubMed ID | 27063844 |
| Mgi Jnum | J:236897 | Mgi Id | MGI:5810053 |
| Doi | 10.1038/ncomms11366 | Citation | Fansa EK, et al. (2016) PDE6delta-mediated sorting of INPP5E into the cilium is determined by cargo-carrier affinity. Nat Commun 7:11366 |
| abstractText | The phosphodiesterase 6 delta subunit (PDE6delta) shuttles several farnesylated cargos between membranes. The cargo sorting mechanism between cilia and other compartments is not understood. Here we show using the inositol polyphosphate 5'-phosphatase E (INPP5E) and the GTP-binding protein (Rheb) that cargo sorting depends on the affinity towards PDE6delta and the specificity of cargo release. High-affinity cargo is exclusively released by the ciliary transport regulator Arl3, while low-affinity cargo is released by Arl3 and its non-ciliary homologue Arl2. Structures of PDE6delta/cargo complexes reveal the molecular basis of the sorting signal which depends on the residues at the -1 and -3 positions relative to farnesylated cysteine. Structure-guided mutation allows the generation of a low-affinity INPP5E mutant which loses exclusive ciliary localization. We postulate that the affinity to PDE6delta and the release by Arl2/3 in addition to a retention signal are the determinants for cargo sorting and enrichment at its destination. |
