| First Author | Conduit SE | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 7181 |
| PubMed ID | 39168978 | Mgi Jnum | J:353433 |
| Mgi Id | MGI:7713789 | Doi | 10.1038/s41467-024-51354-1 |
| Citation | Conduit SE, et al. (2024) A class I PI3K signalling network regulates primary cilia disassembly in normal physiology and disease. Nat Commun 15(1):7181 |
| abstractText | Primary cilia are antenna-like organelles which sense extracellular cues and act as signalling hubs. Cilia dysfunction causes a heterogeneous group of disorders known as ciliopathy syndromes affecting most organs. Cilia disassembly, the process by which cells lose their cilium, is poorly understood but frequently observed in disease and upon cell transformation. Here, we uncover a role for the PI3Kalpha signalling enzyme in cilia disassembly. Genetic PI3Kalpha-hyperactivation, as observed in PIK3CA-related overgrowth spectrum (PROS) and cancer, induced a ciliopathy-like phenotype during mouse development. Mechanistically, PI3Kalpha and PI3Kbeta produce the PIP(3) lipid at the cilia transition zone upon disassembly stimulation. PI3Kalpha activation initiates cilia disassembly through a kinase signalling axis via the PDK1/PKCiota kinases, the CEP170 centrosomal protein and the KIF2A microtubule-depolymerising kinesin. Our data suggest diseases caused by PI3Kalpha-activation may be considered 'Disorders with Ciliary Contributions', a recently-defined subset of ciliopathies in which some, but not all, of the clinical manifestations result from cilia dysfunction. |
