Dynamic crotonylation of EB1 by TIP60 ensures accurate spindle positioning in mitosis.
Nat Chem Biol
; 17(12): 1314-1323, 2021 12.
Article
en En
| MEDLINE
| ID: mdl-34608293
ABSTRACT
Spindle position control is essential for cell fate determination and organogenesis. Early studies indicate the essential role of the evolutionarily conserved Gαi/LGN/NuMA network in spindle positioning. However, the regulatory mechanisms that couple astral microtubules dynamics to the spindle orientation remain elusive. Here we delineated a new mitosis-specific crotonylation-regulated astral microtubule-EB1-NuMA interaction in mitosis. EB1 is a substrate of TIP60, and TIP60-dependent crotonylation of EB1 tunes accurate spindle positioning in mitosis. Mechanistically, TIP60 crotonylation of EB1 at Lys66 forms a dynamic link between accurate attachment of astral microtubules to the lateral cell cortex defined by NuMA-LGN and fine tune of spindle positioning. Real-time imaging of chromosome movements in HeLa cells expressing genetically encoded crotonylated EB1 revealed the importance of crotonylation dynamics for accurate control of spindle orientation during metaphase-anaphase transition. These findings delineate a general signaling cascade that integrates protein crotonylation with accurate spindle positioning for chromosome stability in mitosis.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas de Ciclo Celular
/
Lisina Acetiltransferasa 5
/
Proteínas Asociadas a Microtúbulos
/
Microtúbulos
/
Huso Acromático
Límite:
Humans
Idioma:
En
Revista:
Nat Chem Biol
Asunto de la revista:
BIOLOGIA
/
QUIMICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
China