Cep97 and CP110 suppress a cilia assembly program.
Mammalian centrioles play a dynamic role in centrosome function, but they also have the capacity to nucleate the assembly of cilia. Although controls must exist to specify these different fates, the key regulators remain largely undefined. We have purified complexes associated with CP110, a protein that plays an essential role in centrosome duplication and cytokinesis, and have identified a previously uncharacterized protein, Cep97, that recruits CP110 to centrosomes. Depletion of Cep97 or expression of dominant-negative mutants results in CP110 disappearance from centrosomes, spindle defects, and polyploidy. Remarkably, loss of Cep97 or CP110 promotes primary cilia formation in growing cells, and enforced expression of CP110 in quiescent cells suppresses their ability to assemble cilia, suggesting that Cep97 and CP110 collaborate to inhibit a ciliogenesis program. Identification of Cep97 and other genes involved in regulation of cilia assembly may accelerate our understanding of human ciliary diseases, including renal disease and retinal degeneration.
Spektor
Alexander
A
Department of Pathology and NYU Cancer Institute, New York University School of Medicine, Smilow Research Center, 522 First Avenue, New York, NY 10016, USA.
Tsang
William Y
WY
Khoo
David
D
Dynlacht
Brian David
BD
D000818:Animals; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002502:Centrioles / Q000502:physiology; D018385:Centrosome / Q000502:physiology; D002923:Cilia; D048749:Cytokinesis / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D041681:NIH 3T3 Cells; D010750:Phosphoproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D011123:Polyploidy; D011233:Precipitin Tests; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D008941:Spindle Apparatus / Q000473:pathology
C467559:CCP110 protein, human; C523555:CEP97 protein, human; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins