title: CEP162 is an axoneme-recognition protein promoting ciliary transition zone assembly at the cilia base.
abstract: The transition zone is a specialized compartment found at the base of cilia, adjacent to the centriole distal end, where axonemal microtubules are heavily crosslinked to the surrounding membrane to form a barrier that gates the ciliary compartment. A number of ciliopathy molecules have been found to associate with the transition zone, but factors that directly recognize axonemal microtubules to specify transition zone assembly at the cilia base remain unclear. Here, through quantitative centrosome proteomics, we identify an axoneme-associated protein, CEP162 (KIAA1009), tethered specifically at centriole distal ends to promote transition zone assembly. CEP162 interacts with core transition zone components, and mediates their association with microtubules. Loss of CEP162 arrests ciliogenesis at the stage of transition zone assembly. Abolishing its centriolar tethering, however, allows CEP162 to stay on the growing end of the axoneme and ectopically assemble transition zone components at cilia tips. This generates extra-long cilia with strikingly swollen tips that actively release ciliary contents into the extracellular environment. CEP162 is thus an axoneme-recognition protein pre-tethered at centriole distal ends before ciliogenesis to promote and restrict transition zone formation specifically at the cilia base.
authors: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors: Won-Jing
authors: WJ
authors: Wang
authors: Hwee Goon
authors: HG
authors: Tay
authors: Rajesh
authors: R
authors: Soni
authors: Geoffrey S
authors: GS
authors: Perumal
authors: Mary G
authors: MG
authors: Goll
authors: Frank P
authors: FP
authors: Macaluso
authors: John M
authors: JM
authors: Asara
authors: Jeffrey D
authors: JD
authors: Amack
authors: Meng-Fu Bryan
authors: MF
authors: Tsou
mesh_terms: D016475:3T3 Cells; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D054468:Axoneme / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D002502:Centrioles / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism; D002923:Cilia / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008868:Microtubule Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; C493903:Cep290 protein, human; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000251:Adenosine Triphosphatases; C509844:CEP162 protein, human
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