An ordered pattern of Ana2 phosphorylation by Plk4 is required for centriole assembly
| Autor: | Daniel W. Buster, Cody J. Boese, Natalie A. Hollingsworth, Kevin C. Slep, John M. Ryniawec, Amy E. Byrnes, Gregory C. Rogers, Christopher W. Brownlee, Brian J. Galletta, Tiffany A. McLamarrah, Nasser M. Rusan |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
PLK4 Centriole sports Mutant Cell Cycle Proteins Biology Protein Serine-Threonine Kinases Article Cell Line 03 medical and health sciences Procentriole 0302 clinical medicine Animals Drosophila Proteins Protein Interaction Domains and Motifs Phosphorylation Kinase activity Research Articles Centrioles 030304 developmental biology 0303 health sciences Kinase Chemistry Cell Cycle Cell Biology Cell biology sports.league Protein Transport enzymes and coenzymes (carbohydrates) 030104 developmental biology Drosophila melanogaster Protein kinase domain Mutation Microtubule-Associated Proteins 030217 neurology & neurosurgery Protein Binding Signal Transduction Centriole assembly |
| Zdroj: | The Journal of Cell Biology |
| DOI: | 10.1101/240374 |
| Popis: | Centriole duplication is tightly regulated throughout the cell cycle to ensure one duplication event per centriole. McLamarrah et al. show that a stepwise pattern of Ana2 phosphorylation by Plk4 facilitates proper centriole duplication. Polo-like kinase 4 (Plk4) initiates an early step in centriole assembly by phosphorylating Ana2/STIL, a structural component of the procentriole. Here, we show that Plk4 binding to the central coiled-coil (CC) of Ana2 is a conserved event involving Polo-box 3 and a previously unidentified putative CC located adjacent to the kinase domain. Ana2 is then phosphorylated along its length. Previous studies showed that Plk4 phosphorylates the C-terminal STil/ANa2 (STAN) domain of Ana2/STIL, triggering binding and recruitment of the cartwheel protein Sas6 to the procentriole assembly site. However, the physiological relevance of N-terminal phosphorylation was unknown. We found that Plk4 first phosphorylates the extreme N terminus of Ana2, which is critical for subsequent STAN domain modification. Phosphorylation of the central region then breaks the Plk4–Ana2 interaction. This phosphorylation pattern is important for centriole assembly and integrity because replacement of endogenous Ana2 with phospho-Ana2 mutants disrupts distinct steps in Ana2 function and inhibits centriole duplication. |
| Databáze: | OpenAIRE |
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