title: WDR8 is a centriolar satellite and centriole-associated protein that promotes ciliary vesicle docking during ciliogenesis.
abstract: Ciliogenesis initiates at the mother centriole through a series of events that include membrane docking, displacement of cilia-inhibitory proteins and axoneme elongation. Centriolar proteins, in particular at distal and subdistal appendages, carry out these functions. Recently, cytoplasmic complexes named centriolar satellites have also been shown to promote ciliogenesis. Little is known about the functional and molecular relationship between appendage proteins, satellites and cilia biogenesis. Here, we identified the WD-repeat protein 8 (WDR8, also known as WRAP73) as a satellite and centriolar component. We show that WDR8 interacts with the satellite proteins SSX2IP and PCM1 as well as the centriolar proximal end component Cep135. Cep135 is required for the recruitment of WDR8 to centrioles. Depletion experiments revealed that WDR8 and Cep135 have strongly overlapping functions in ciliogenesis. Both are indispensable for ciliary vesicle docking to the mother centriole and for unlocking the distal end of the mother centriole from the ciliary inhibitory complex CP110-Cep97. Our data thus point to an important function of centriolar proximal end proteins in ciliary membrane biogenesis, and establish WDR8 and Cep135 as two factors that are essential for the initial steps of ciliation.
authors.affiliation: Centre for Organismal Studies (COS), Im Neuenheimer Feld 230, Heidelberg 69120, Germany Division of Centrosomes and Cilia, German Cancer Research Centre (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, Heidelberg 69120, Germany.
authors.forename: Bahtiyar
authors.initials: B
authors.lastname: Kurtulmus
authors.affiliation: Division of Centrosomes and Cilia, German Cancer Research Centre (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, Heidelberg 69120, Germany Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, Heidelberg 69120, Germany.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Wang
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, Heidelberg 69120, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruppert
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, Heidelberg 69120, Germany.
authors.forename: Annett
authors.initials: A
authors.lastname: Neuner
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, Heidelberg 69120, Germany.
authors.forename: Berati
authors.initials: B
authors.lastname: Cerikan
authors.affiliation: Centre for Organismal Studies (COS), Im Neuenheimer Feld 230, Heidelberg 69120, Germany Division of Centrosomes and Cilia, German Cancer Research Centre (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, Heidelberg 69120, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Viol
authors.affiliation: Division of Centrosomes and Cilia, German Cancer Research Centre (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, Heidelberg 69120, Germany.
authors.forename: Rafael
authors.initials: R
authors.lastname: Dueñas-Sánchez
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, Heidelberg 69120, Germany gislene.pereira@cos.uni-heidelberg.de o.gruss@uni-bonn.de.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Gruss
authors.affiliation: Centre for Organismal Studies (COS), Im Neuenheimer Feld 230, Heidelberg 69120, Germany Division of Centrosomes and Cilia, German Cancer Research Centre (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, Heidelberg 69120, Germany gislene.pereira@cos.uni-heidelberg.de o.gruss@uni-bonn.de.
authors.forename: Gislene
authors.initials: G
authors.lastname: Pereira
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D054468:Axoneme / Q000378:metabolism / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002502:Centrioles / Q000378:metabolism* / Q000502:physiology; D002923:Cilia / Q000378:metabolism* / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009024:Morphogenesis / Q000502:physiology*; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*
chemical_list: D001324:Autoantigens; C467559:CCP110 protein, human; C534330:CEP135 protein, human; C523555:CEP97 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C086074:PCM1 protein, human; D010750:Phosphoproteins; D011506:Proteins; C000605616:SSX2IP protein, human; C433889:WRAP73 protein, human
keywords: Basal body; Centrosomes; Cep135; Cilia; SSX2IP; Satellites; WDR8; WRAP73