title: The CP110-interacting proteins Talpid3 and Cep290 play overlapping and distinct roles in cilia assembly.
abstract: We have identified Talpid3/KIAA0586 as a component of a CP110-containing protein complex important for centrosome and cilia function. Talpid3 assembles a ring-like structure at the extreme distal end of centrioles. Ablation of Talpid3 resulted in an aberrant distribution of centriolar satellites involved in protein trafficking to centrosomes as well as cilia assembly defects, reminiscent of loss of Cep290, another CP110-associated protein. Talpid3 depletion also led to mislocalization of Rab8a, a small GTPase thought to be essential for ciliary vesicle formation. Expression of activated Rab8a suppressed cilia assembly defects provoked by Talpid3 depletion, suggesting that Talpid3 affects cilia formation through Rab8a recruitment and/or activation. Remarkably, ultrastructural analyses showed that Talpid3 is required for centriolar satellite dispersal, which precedes the formation of mature ciliary vesicles, a process requiring Cep290. These studies suggest that Talpid3 and Cep290 play overlapping and distinct roles in ciliary vesicle formation through regulation of centriolar satellite accretion and Rab8a.
authors.affiliation: Department of Pathology and Cancer Institute, Smilow Research Center, New York University School of Medicine, New York, NY 10016.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Sehyun
authors.initials: S
authors.lastname: Kim
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.forename: Takanari
authors.initials: T
authors.lastname: Inoue
authors.forename: Brian David
authors.initials: BD
authors.lastname: Dynlacht
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D002502:Centrioles / Q000378:metabolism; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D003598:Cytoskeletal Proteins; D049452:Green Fluorescent Proteins / Q000032:analysis; D057809:HEK293 Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000032:analysis; D020691:rab GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; C493903:Cep290 protein, human; D003598:Cytoskeletal Proteins; C587687:KIAA0586 protein, human; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C082377:RAB8A protein, human; D020691:rab GTP-Binding Proteins