Importin α/ß promote Kif18B microtubule association and enhance microtubule destabilization activity.
Mol Biol Cell
; 34(4): ar30, 2023 04 01.
Article
em En
| MEDLINE
| ID: mdl-36790918
ABSTRACT
Tight regulation of microtubule (MT) dynamics is necessary for proper spindle assembly and chromosome segregation. The MT destabilizing Kinesin-8, Kif18B, controls astral MT dynamics and spindle positioning. Kif18B interacts with importin α/ß as well as with the plus-tip tracking protein EB1, but how these associations modulate Kif18B is not known. We mapped the key binding sites on Kif18B, made residue-specific mutations, and assessed their impact on Kif18B function. Blocking EB1 interaction disrupted Kif18B MT plus-end accumulation and inhibited its ability to control MT length on monopolar spindles in cells. Blocking importin α/ß interaction disrupted Kif18B localization without affecting aster size. In vitro, importin α/ß increased Kif18B MT association by increasing the on-rate and decreasing the off-rate from MTs, which stimulated MT destabilization. In contrast, EB1 promoted MT destabilization without increasing lattice binding in vitro, which suggests that EB1 and importin α/ß have distinct roles in the regulation of Kif18B-mediated MT destabilization. We propose that importin α/ß spatially modulate Kif18B association with MTs to facilitate its MT destabilization activity. Our results suggest that Ran regulation is important not only to control molecular motor function near chromatin but also to provide a spatial control mechanism to modulate MT binding of nuclear localization signal-containing spindle assembly factors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carioferinas
/
Alfa Carioferinas
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article