title: Dimerization of CPAP orchestrates centrosome cohesion plasticity.
abstract: Centrosome cohesion and segregation are accurately regulated to prevent an aberrant separation of duplicated centrosomes and to ensure the correct formation of bipolar spindles by a tight coupling with cell cycle machinery. CPAP is a centrosome protein with five coiled-coil domains and plays an important role in the control of brain size in autosomal recessive primary microcephaly. Previous studies showed that CPAP interacts with tubulin and controls centriole length. Here, we reported that CPAP forms a homodimer during interphase, and the fifth coiled-coil domain of CPAP is required for its dimerization. Moreover, this self-interaction is required for maintaining centrosome cohesion and preventing the centrosome from splitting before the G(2)/M phase. Our biochemical studies show that CPAP forms homodimers in vivo. In addition, both monomeric and dimeric CPAP are required for accurate cell division, suggesting that the temporal dynamics of CPAP homodimerization is tightly regulated during the cell cycle. Significantly, our results provide evidence that CPAP is phosphorylated during mitosis, and this phosphorylation releases its intermolecular interaction. Taken together, these results suggest that cell cycle-regulated phosphorylation orchestrates the dynamics of CPAP molecular interaction and centrosome splitting to ensure genomic stability in cell division.
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei 230027, China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Zhao
authors.forename: Changjiang
authors.initials: C
authors.lastname: Jin
authors.forename: Youjun
authors.initials: Y
authors.lastname: Chu
authors.forename: Chris
authors.initials: C
authors.lastname: Varghese
authors.forename: Shasha
authors.initials: S
authors.lastname: Hua
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.forename: Yong
authors.initials: Y
authors.lastname: Miao
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: David
authors.initials: D
authors.lastname: Mann
authors.forename: Xia
authors.initials: X
authors.lastname: Ding
authors.forename: Jiancun
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dou
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
mesh_terms: D002455:Cell Division / Q000502:physiology; D018385:Centrosome / Q000737:chemistry* / Q000502:physiology*; D019281:Dimerization; D006367:HeLa Cells; D006801:Humans; D007399:Interphase / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008970:Molecular Weight; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D008941:Spindle Apparatus / Q000737:chemistry / Q000502:physiology; D014162:Transfection
chemical_list: C414735:CENPJ protein, human; D008869:Microtubule-Associated Proteins