{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Weber J"],"funding":["European Molecular Biology Organization","Danmarks Frie Forskningsfond","Wellcome Trust","Novo Nordisk Fonden"],"pagination":["1133-1141.e4"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617963"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["34(5)"],"pubmed_abstract":["The outer corona plays an essential role at the onset of mitosis by expanding to maximize microtubule attachment to kinetochores.1,2 The low-density structure of the corona forms through the expansion of unattached kinetochores. It comprises the RZZ complex, the dynein adaptor Spindly, the plus-end directed microtubule motor centromere protein E (CENP-E), and the Mad1/Mad2 spindle-assembly checkpoint proteins.3,4,5,6,7,8,9,10 CENP-E specifically associates with unattached kinetochores to facilitate chromosome congression,11,12,13,14,15,16 interacting with BubR1 at the kinetochore through its C-terminal region (2091-2358).17,18,19,20,21 We recently showed that CENP-E recruitment to BubR1 at the kinetochores is both rapid and essential for correct chromosome alignment. However, CENP-E is also recruited to the outer corona by a second, slower pathway that is currently undefined.19 Here, we show that BubR1-independent localization of CENP-E is mediated by a conserved loop that is essential for outer-corona targeting. We provide a structural model of the entire CENP-E kinetochore-targeting domain combining X-ray crystallography and Alphafold2. We reveal that maximal recruitment of CENP-E to unattached kinetochores critically depends on BubR1 and the outer corona, including dynein. Ectopic expression of the CENP-E C-terminal domain recruits the RZZ complex, Mad1, and Spindly, and prevents kinetochore biorientation in cells. We propose that BubR1-recruited CENP-E, in addition to its essential role in chromosome alignment to the metaphase plate, contributes to the recruitment of outer corona proteins through interactions with the CENP-E corona-targeting domain to facilitate the rapid capture of microtubules for efficient chromosome alignment and mitotic progression."],"journal":["Current biology : CB"],"pubmed_title":["A conserved CENP-E region mediates BubR1-independent recruitment to the outer corona at mitotic onset."],"pmcid":["PMC7617963"],"funding_grant_id":["219413","DFF-3101-00075","207430","207430/Z/17/Z","NNF19OC0058504","203149"],"pubmed_authors":["Eibes S","Legal T","Lezcano AP","Gluszek-Kustusz A","Welburn JPI","Paterson C","Weber J","Davies OR","Barisic M"],"additional_accession":[]},"is_claimable":false,"name":"A conserved CENP-E region mediates BubR1-independent recruitment to the outer corona at mitotic onset.","description":"The outer corona plays an essential role at the onset of mitosis by expanding to maximize microtubule attachment to kinetochores.1,2 The low-density structure of the corona forms through the expansion of unattached kinetochores. It comprises the RZZ complex, the dynein adaptor Spindly, the plus-end directed microtubule motor centromere protein E (CENP-E), and the Mad1/Mad2 spindle-assembly checkpoint proteins.3,4,5,6,7,8,9,10 CENP-E specifically associates with unattached kinetochores to facilitate chromosome congression,11,12,13,14,15,16 interacting with BubR1 at the kinetochore through its C-terminal region (2091-2358).17,18,19,20,21 We recently showed that CENP-E recruitment to BubR1 at the kinetochores is both rapid and essential for correct chromosome alignment. However, CENP-E is also recruited to the outer corona by a second, slower pathway that is currently undefined.19 Here, we show that BubR1-independent localization of CENP-E is mediated by a conserved loop that is essential for outer-corona targeting. We provide a structural model of the entire CENP-E kinetochore-targeting domain combining X-ray crystallography and Alphafold2. We reveal that maximal recruitment of CENP-E to unattached kinetochores critically depends on BubR1 and the outer corona, including dynein. Ectopic expression of the CENP-E C-terminal domain recruits the RZZ complex, Mad1, and Spindly, and prevents kinetochore biorientation in cells. We propose that BubR1-recruited CENP-E, in addition to its essential role in chromosome alignment to the metaphase plate, contributes to the recruitment of outer corona proteins through interactions with the CENP-E corona-targeting domain to facilitate the rapid capture of microtubules for efficient chromosome alignment and mitotic progression.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-03-10T23:05:59.111Z","creation":"2025-08-12T03:05:01.955Z"},"accession":"S-EPMC7617963","cross_references":{"pubmed":["38354735"],"doi":["10.1016/j.cub.2024.01.042"]}}