Multivalency of NDC80 in the outer kinetochore is essential to track shortening microtubules and generate forces.
Elife
; 72018 04 09.
Article
en En
| MEDLINE
| ID: mdl-29629870
Presence of multiple copies of the microtubule-binding NDC80 complex is an evolutionary conserved feature of kinetochores, points of attachment of chromosomes to spindle microtubules. This may enable multivalent attachments to microtubules, with implications that remain unexplored. Using recombinant human kinetochore components, we show that while single NDC80 complexes do not track depolymerizing microtubules, reconstituted particles containing the NDC80 receptor CENP-T bound to three or more NDC80 complexes do so effectively, as expected for a kinetochore force coupler. To study multivalency systematically, we engineered modules allowing incremental addition of NDC80 complexes. The modules' residence time on microtubules increased exponentially with the number of NDC80 complexes. Modules with two or more complexes tracked depolymerizing microtubules with increasing efficiencies, and stalled and rescued microtubule depolymerization in a force-dependent manner when conjugated to cargo. Our observations indicate that NDC80, rather than through biased diffusion, tracks depolymerizing microtubules by harnessing force generated during microtubule disassembly.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
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Proteínas Cromosómicas no Histona
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Cinetocoros
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Proteínas Asociadas a Microtúbulos
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Microtúbulos
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Mitosis
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Huso Acromático
Límite:
Humans
Idioma:
En
Revista:
Elife
Año:
2018
Tipo del documento:
Article
País de afiliación:
Países Bajos