Nek5 promotes centrosome integrity in interphase and loss of centrosome cohesion in mitosis
| Autor: | Navdeep K. Sahota, Suzanna L. Prosser, Andrew M. Fry, Ciaran G. Morrison, Laurence Pelletier |
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| Rok vydání: | 2015 |
| Předmět: |
separation
animal structures family Centriole disjunction Molecular Sequence Data protein-kinase Cell Cycle Proteins Nerve Tissue Proteins Centrosome cycle Spindle Apparatus substrate Biology Microtubules Spindle pole body 03 medical and health sciences 0302 clinical medicine c-nap1 Tubulin Report Humans Antigens Interphase Research Articles 030304 developmental biology Microtubule nucleation Centrosome 0303 health sciences Base Sequence Intracellular Signaling Peptides and Proteins Microtubule organizing center Cell Biology linker Cell biology Cytoskeletal Proteins HEK293 Cells cell-cycle 030220 oncology & carcinogenesis cep68 Rootletin Centrosome separation Protein Kinases HeLa Cells |
| Zdroj: | The Journal of Cell Biology |
| Popis: | The Nek5 protein kinase contributes not only to uncoupling of the centrosome linker but also to integrity of the pericentriolar material and centrosomal microtubule nucleation, which together ensure the timely separation of centrosomes during early mitosis. Nek5 is a poorly characterized member of the NIMA-related kinase family, other members of which play roles in cell cycle progression and primary cilia function. Here, we show that Nek5, similar to Nek2, localizes to the proximal ends of centrioles. Depletion of Nek5 or overexpression of kinase-inactive Nek5 caused unscheduled separation of centrosomes in interphase, a phenotype also observed upon overexpression of active Nek2. However, separated centrosomes that resulted from Nek5 depletion remained relatively close together, exhibited excess recruitment of the centrosome linker protein rootletin, and had reduced levels of Nek2. In addition, Nek5 depletion led to loss of PCM components, including γ-tubulin, pericentrin, and Cdk5Rap2, with centrosomes exhibiting reduced microtubule nucleation. Upon mitotic entry, Nek5-depleted cells inappropriately retained centrosome linker components and exhibited delayed centrosome separation and defective chromosome segregation. Hence, Nek5 is required for the loss of centrosome linker proteins and enhanced microtubule nucleation that lead to timely centrosome separation and bipolar spindle formation in mitosis. |
| Databáze: | OpenAIRE |
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