0000000000704210
AUTHOR
Quanlong Lu
Primary Cilium Mediated Retinal Pigment Epithelium Maturation is Retarded in Ciliopathy Patient Cells
Primary cilia are sensory organelles that protrude from the cell membrane. Cilia defects cause ciliopathy disorders with retinal degeneration as a prominent phenotype. Here, we demonstrate that the retinal pigment epithelium (RPE), essential for photoreceptor development and function, requires a functional primary cilium for complete maturation, and RPE maturation defects in ciliopathies precede photoreceptor development. Pharmacologically enhanced ciliogenesis in wildtype induced pluripotent stem cells (iPSCs)-RPE leads to fully-mature and functional cells. Whereas, ciliopathy patient-derived iPSCs-RPE and wildtype iPSC-RPE with a knockdown of ciliary-trafficking protein remain immature, w…
A ciliopathy complex builds distal appendages to initiate ciliogenesis
ABSTRACTCells inherit two centrioles, the older of which is uniquely capable of generating a cilium. Using proteomics and super-resolved imaging, we identified a module which we term DISCO (DIStal centriole COmplex). DISCO components CEP90, MNR and OFD1 underlie human ciliopathies. This complex localized to both distal centrioles and centriolar satellites, proteinaceous granules surrounding centrioles. Cells and mice lacking CEP90 or MNR did not generate cilia, failed to assemble distal appendages, and did not transduce Hedgehog signals. Disrupting the satellite pools did not affect distal appendage assembly, indicating that it is the centriolar populations of MNR and CEP90 that are critica…
Primary Cilium-Mediated Retinal Pigment Epithelium Maturation Is Disrupted in Ciliopathy Patient Cells
SUMMARY Primary cilia are sensory organelles that protrude from the cell membrane. Defects in the primary cilium cause ciliopathy disorders, with retinal degeneration as a prominent phenotype. Here, we demonstrate that the retinal pigment epithelium (RPE), essential for photoreceptor development and function, requires a functional primary cilium for complete maturation and that RPE maturation defects in ciliopathies precede photoreceptor degeneration. Pharmacologically enhanced ciliogenesis in wild-type induced pluripotent stem cells (iPSC)-RPE leads to fully mature and functional cells. In contrast, ciliopathy patient-derived iPSC-RPE and iPSC-RPE with a knockdown of ciliary-trafficking pr…