A conserved CENP-E region mediates BubR1-independent recruitment to the outer corona at mitotic onset
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
A conserved CENP-E region mediates BubR1-independent recruitment to the outer corona at mitotic onset. / Weber, Jeraldine; Legal, Thibault; Lezcano, Alicia Perez; Gluszek-Kustusz, Agata; Paterson, Calum; Eibes, Susana; Barisic, Marin; Davies, Owen R.; Welburn, Julie P.I.
I: Current Biology, Bind 34, Nr. 5, 2024, s. 1133-1141.e4.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - A conserved CENP-E region mediates BubR1-independent recruitment to the outer corona at mitotic onset
AU - Weber, Jeraldine
AU - Legal, Thibault
AU - Lezcano, Alicia Perez
AU - Gluszek-Kustusz, Agata
AU - Paterson, Calum
AU - Eibes, Susana
AU - Barisic, Marin
AU - Davies, Owen R.
AU - Welburn, Julie P.I.
N1 - Publisher Copyright: © 2024 The Author(s)
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - CENP-E motor
KW - centromere
KW - dynein
KW - kinetochore
KW - microtubule
KW - mitosis
KW - motor
KW - outer corona
KW - prometaphase
KW - spindle assembly checkpoint
U2 - 10.1016/j.cub.2024.01.042
DO - 10.1016/j.cub.2024.01.042
M3 - Journal article
C2 - 38354735
AN - SCOPUS:85186979851
VL - 34
SP - 1133-1141.e4
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 5
ER -
ID: 385690574