Journal article
Direct binding of CEP85 to STIL ensures robust PLK4 activation and efficient centriole assembly
- Abstract:
- Centrosomes are required for faithful chromosome segregation during mitosis. They are composed of a centriole pair that recruits and organizes the microtubule-nucleating pericentriolar material. Centriole duplication is tightly controlled in vivo and aberrations in this process are associated with several human diseases, including cancer and microcephaly. Although factors essential for centriole assembly, such as STIL and PLK4, have been identified, the underlying molecular mechanisms that drive this process are incompletely understood. Combining protein proximity mapping with high-resolution structural methods, we identify CEP85 as a centriole duplication factor that directly interacts with STIL through a highly conserved interaction interface involving a previously uncharacterised domain of STIL. Structure-guided mutational analyses in vivo demonstrate that this interaction is essential for efficient centriolar targeting of STIL, PLK4 activation and faithful daughter centriole assembly. Taken together, our results illuminate a molecular mechanism underpinning the spatiotemporal regulation of the early stages of centriole duplication.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 3.8MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-018-04122-x
Authors
+ Ontario Ministry for Research and Innovation
More from this funder
- Funding agency for:
- Pelletier, L
- Grant:
- RE-8
+ Medical Research Council
More from this funder
- Funding agency for:
- Mehmood, S
- Robinson, C
- van Breugel, M
- Grant:
- MR/N020413/1
- MR/N020413/1
- MC_UP_1201/3
- Publisher:
- Nature Publishing Group
- Journal:
- Nature Communications More from this journal
- Volume:
- 9
- Article number:
- 1731
- Publication date:
- 2018-04-30
- Acceptance date:
- 2018-04-05
- DOI:
- ISSN:
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2041-1723
- Pmid:
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29712910
- Language:
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English
- Keywords:
- Pubs id:
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pubs:844985
- UUID:
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uuid:970b7422-f37f-40ec-9fd2-1dcbfa5bc271
- Local pid:
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pubs:844985
- Source identifiers:
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844985
- Deposit date:
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2018-05-03
Terms of use
- Copyright holder:
- © Liu, et al 2018
- Copyright date:
- 2018
- Notes:
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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