Publication

Centriole splitting caused by loss of the centrosomal linker protein c-nap1 reduces centriolar satellite density and impedes centrosome amplification

Flanagan, Anne-Marie
Stavenschi, Elena
Basavaraju, Shivakumar
Gaboriau, David
Hoey, David A.
Morrison, Ciaran G.
Citation
Flanagan, Anne-Marie; Stavenschi, Elena; Basavaraju, Shivakumar; Gaboriau, David; Hoey, David A. Morrison, Ciaran G. (2017). Centriole splitting caused by loss of the centrosomal linker protein c-nap1 reduces centriolar satellite density and impedes centrosome amplification. Molecular Biology of the Cell 28 (6), 736-745
Abstract
Duplication of the centrosomes is a tightly regulated process. Abnormal centrosome numbers can impair cell division and cause changes in how cells migrate. Duplicated centrosomes are held together by a proteinaceous linker made up of rootletin filaments anchored to the centrioles by C-NAP1. This linker is removed in a NEK2A kinase-dependent manner as mitosis begins. To explore C-NAP1 activities in regulating centrosome activities, we used genome editing to ablate it. C-NAP1-null cells were viable and had an increased frequency of premature centriole separation, accompanied by reduced density of the centriolar satellites, with reexpression of C-NAP1 rescuing both phenotypes. We found that the primary cilium, a signaling structure that arises from the mother centriole docked to the cell membrane, was intact in the absence of C-NAP1, although components of the ciliary rootlet were aberrantly localized away from the base of the cilium. C-NAP1-deficient cells were capable of signaling through the cilium, as determined by gene expression analysis after fluid flow-induced shear stress and the relocalization of components of the Hedgehog pathway. Centrosome amplification induced by DNA damage or by PLK4 or CDK2 overexpression was markedly reduced in the absence of C-NAP1. We conclude that centriole splitting reduces the local density of key centriolar precursors to impede overduplication.
Funder
Publisher
American Society for Cell Biology (ASCB)
Publisher DOI
10.1091/mbc.e16-05-0325
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland