| First Author | Luo C | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 9 | Pages | 9945-9958 |
| PubMed ID | 31157564 | Mgi Jnum | J:293981 |
| Mgi Id | MGI:6452708 | Doi | 10.1096/fj.201900338R |
| Citation | Luo C, et al. (2019) Protein phosphatase 1alpha interacts with a novel ciliary targeting sequence of polycystin-1 and regulates polycystin-1 trafficking. FASEB J 33(9):9945-9958 |
| abstractText | Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder causing renal failure. Mutations of polycystic kidney disease 1 (PKD1) account for most ADPKD cases. Defective ciliary localization of polycystin-1 (PC1), a large integral membrane protein encoded by PKD1, underlies the pathogenesis of a subgroup of patients with ADPKD. However, the mechanisms by which PC1 and other ciliary proteins traffic to the primary cilium remain poorly understood. A ciliary targeting sequence (CTS) that resides in ciliary receptors is considered to function in the process. It has been reported that the VxP motif in the intracellular C-terminal tail of PC1 functions as a CTS in an ADP ribosylation factor 4 (Arf4)/ArfGAP with SH3 domain, ankyrin repeat and PH domain 1 (ASAP1)-dependent manner. However, other recent studies have revealed that this motif is dispensable for PC1 trafficking to cilia. In this study, we identified a novel CTS consisting of 8 residues (RHKVRFEG) in the PC1 C tail. We found that this motif is sufficient to bind protein phosphatase 1 (PP1)alpha, a ubiquitously expressed phosphatase in the phosphoprotein phosphatase (PPP) family. Mutations in this CTS motif disrupt binding with PP1alpha and impair ciliary localization of PC1. Additionally, short hairpin RNA-mediated knockdown of PP1alpha results in reduced ciliary localization of PC1 and elongated cilia, suggesting a role for PP1alpha in the regulation of ciliary structure and function.-Luo, C., Wu, M., Su, X., Yu, F., Brautigan, D. L., Chen, J., Zhou, J. Protein phosphatase 1alpha interacts with a novel ciliary targeting sequence of polycystin-1 and regulates polycystin-1 trafficking. |
