Polley, Soumitra; Müschenborn, Helen; Terbeck, Melina; De Antoni, Anna; Vetter, Ingrid R; Dogterom, Marileen; Musacchio, Andrea; Volkov, Vladimir A; Huis in 't Veld, Pim J:
Stable kinetochore-microtubule attachment requires loop-dependent Ndc80-Ndc80 binding
In: The EMBO Journal, Vol. 42 (2023), No. 13, Article e112504
2023article/chapter in journalOA Hybrid
MedicineScientific institutes » Center of Medical Biotechnology (ZMB)
Related: 1 publication(s)
Title in English:
Stable kinetochore-microtubule attachment requires loop-dependent Ndc80-Ndc80 binding
Author:
Polley, Soumitra
;
Müschenborn, Helen
;
Terbeck, Melina
;
De Antoni, Anna
;
Vetter, Ingrid R
;
Dogterom, Marileen
;
Musacchio, AndreaUDE
LSF ID
57733
ORCID
0000-0003-2362-8784ORCID iD
Other
connected with university
corresponding author
;
Volkov, Vladimir A
Other
corresponding author
;
Huis in 't Veld, Pim J
Other
corresponding author
Year of publication:
2023
Open Access?:
OA Hybrid
Web of Science ID
PubMed ID
Scopus ID
Language of text:
English
Keyword, Topic:
chromosome segregation ; kinetochore ; microtubule ; Ndc80 ; spindle assembly checkpoint

Abstract in English:

During cell division, kinetochores link chromosomes to spindle microtubules. The Ndc80 complex, a crucial microtubule binder, populates each kinetochore with dozens of copies. Whether adjacent Ndc80 complexes cooperate to promote microtubule binding remains unclear. Here we demonstrate that the Ndc80 loop, a short sequence that interrupts the Ndc80 coiled-coil at a conserved position, folds into a more rigid structure than previously assumed and promotes direct interactions between full-length Ndc80 complexes on microtubules. Mutations in the loop impair these Ndc80-Ndc80 interactions, prevent the formation of force-resistant kinetochore-microtubule attachments, and cause cells to arrest in mitosis for hours. This arrest is not due to an inability to recruit the kinetochore-microtubule stabilizing SKA complex and cannot be overridden by mutations in the Ndc80 tail that strengthen microtubule attachment. Thus, loop-mediated organization of adjacent Ndc80 complexes is crucial for stable end-on kinetochore-microtubule attachment and spindle assembly checkpoint satisfaction.