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, Jg. 42 (2023), Heft 13, Artikel e112504
2023Artikel/Aufsatz in ZeitschriftOA Hybrid
MedizinForschungszentren » Zentrum für Medizinische Biotechnologie (ZMB)
Damit verbunden: 1 Publikation(en)
Titel in Englisch:
Stable kinetochore-microtubule attachment requires loop-dependent Ndc80-Ndc80 binding
Autor*in:
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
Sonstiges
der Hochschule zugeordnete*r Autor*in
korrespondierende*r Autor*in
;
Volkov, Vladimir A
Sonstiges
korrespondierende*r Autor*in
;
Huis in 't Veld, Pim J
Sonstiges
korrespondierende*r Autor*in
Erscheinungsjahr:
2023
Open Access?:
OA Hybrid
Web of Science ID
PubMed ID
Scopus ID
Sprache des Textes:
Englisch
Schlagwort, Thema:
chromosome segregation ; kinetochore ; microtubule ; Ndc80 ; spindle assembly checkpoint

Abstract in Englisch:

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.