title: Tethering of an E3 ligase by PCM1 regulates the abundance of centrosomal KIAA0586/Talpid3 and promotes ciliogenesis.
abstract: To elucidate the role of centriolar satellites in ciliogenesis, we deleted the gene encoding the PCM1 protein, an integral component of satellites. PCM1 null human cells show marked defects in ciliogenesis, precipitated by the loss of specific proteins from satellites and their relocation to centrioles. We find that an amino-terminal domain of PCM1 can restore ciliogenesis and satellite localization of certain proteins, but not others, pinpointing unique roles for PCM1 and a group of satellite proteins in cilium assembly. Remarkably, we find that PCM1 is essential for tethering the E3 ligase, Mindbomb1 (Mib1), to satellites. In the absence of PCM1, Mib1 destabilizes Talpid3 through poly-ubiquitylation and suppresses cilium assembly. Loss of PCM1 blocks ciliogenesis by abrogating recruitment of ciliary vesicles associated with the Talpid3-binding protein, Rab8, which can be reversed by inactivating Mib1. Thus, PCM1 promotes ciliogenesis by tethering a key E3 ligase to satellites and restricting it from centrioles.
authors.affiliation: Department of Pathology, New York University Cancer Institute, New York University School of Medicine, New York, United States.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, New York University Cancer Institute, New York University School of Medicine, New York, United States.
authors.forename: Kwanwoo
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Pathology, New York University Cancer Institute, New York University School of Medicine, New York, United States.
authors.forename: Ryan
authors.initials: R
authors.lastname: Malonis
authors.affiliation: Department of Pathology, New York University Cancer Institute, New York University School of Medicine, New York, United States.
authors.forename: Irma
authors.initials: I
authors.lastname: Sanchez
authors.affiliation: Department of Pathology, New York University Cancer Institute, New York University School of Medicine, New York, United States.
authors.forename: Brian D
authors.identifier: 0000-0001-9485-512X
authors.initials: BD
authors.lastname: Dynlacht
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002502:Centrioles / Q000378:metabolism*; D002923:Cilia; D006801:Humans; D051379:Mice; D001678:Organelle Biogenesis; D011485:Protein Binding; D021381:Protein Transport; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D001324:Autoantigens; D018797:Cell Cycle Proteins; C587687:KIAA0586 protein, human; C086074:PCM1 protein, human; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases
keywords: E3 ligase; cell biology; centriolar satellites; ciliogenesis; human