Supernumerary centrosomes nucleate extra cilia and compromise primary cilium signaling.

摘要: The primary cilium is a nexus of cell signaling, and ciliary dysfunction associated with polycystic kidney disease, retinal degeneration, polydactyly, neural tube defects, obesity (ciliopathies). Signaling molecules for cilium-associated pathways are concentrated in the cilium, this essential efficient signaling. Cilia nucleated from centrioles, aberrant centriole numbers seen many cancers some ciliopathies. We tested effect supernumerary centrioles on function found that cells extra often formed more than one had reduced concentration Smoothened response to Sonic hedgehog stimulation, Shh pathway transcriptional activation. This dilution phenotype was also observed serotonin receptor Htr6, fibrocystin PKHD1, Arl13b. presence cilia disrupted epithelial organization 3D spheroid culture. Cells mutant tuberous sclerosis gene Tsc2 diluted protein. In most cells, were clustered shared same pocket, suggesting pocket rate-limiting structure trafficking proteins. Thus, disrupt signaling may contribute disease phenotypes.