CaMKKß-AMPKα2 signaling contributes to mitotic Golgi fragmentation and the G2/M transition in mammalian cells.
Cell Cycle
; 14(4): 598-611, 2015.
Article
em En
| MEDLINE
| ID: mdl-25590814
ABSTRACT
Before a cell enters mitosis, the Golgi apparatus undergoes extensive fragmentation. This is required for the correct partitioning of the Golgi apparatus into daughter cells, and inhibition of this process leads to cell cycle arrest in G2 phase. AMP-activated protein kinase (AMPK) plays critical roles in regulating growth and reprogramming metabolism. Recent studies have suggested that AMPK promotes mitotic progression and Golgi disassembly, and that this seems independent of the cellular energy status. However, the molecular mechanism underlying these events is not well understood. Here, we show that both treatment with compound C and depletion of AMPKα2 (but not AMPKα1) delays the G2/M transition in synchronized HeLa cells, as evidenced by flow cytometry and mitotic index analysis. Furthermore, knockdown of AMPKα2 specifically delays further fragmentation of isolated Golgi stacks. Interestingly, pAMPKα(Thr172) signals transiently appear in the perinuclear region of late G2/early prophase cells, partially co-localizing with the Golgi matrix protein, GM-130. These Golgi pAMPKα(Thr172) signals were also specifically abolished by AMPKα2 knockdown, indicating specific spatio-temporal activation of AMPKα2 at Golgi complex during late G2/early prophases. We also found that the specific CaMKKß inhibitor, STO-609, reduces the pAMPKα (Thr172) signals in the perinuclear region of G2 phase cells and delays mitotic Golgi fragmentation. Taken together, these data suggest that AMPKα2 is the major catalytic subunit of AMPKα which regulates Golgi fragmentation and G2/M transition, and that the CaMKKß activates AMPKα2 during late G2 phase.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina
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Proteínas Quinases Ativadas por AMP
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Pontos de Checagem da Fase G2 do Ciclo Celular
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Complexo de Golgi
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Mitose
Limite:
Humans
Idioma:
En
Revista:
Cell Cycle
Ano de publicação:
2015
Tipo de documento:
Article