At the onset of mitosis, the Golgi complex undergoes a multi-step fragmentation process that is required for its correct partitioning into the daughter cells. Inhibition of this Golgi fragmentation results in cell-cycle arrest at the G2 stage, thus suggesting that correct inheritance of the Golgi complex is monitored by a 'Golgi mitotic checkpoint'. However, the molecular basis of this G2 block is not known. Here, we show that the G2-specific Golgi fragmentation stage is concomitant with centrosome recruitment and activation of the mitotic kinase Aurora-A, an essential regulator for entry into mitosis. We show that a block of Golgi partitioning impairs centrosome recruitment and activation of Aurora-A, which results in the G2 block of cell-cycle progression. Overexpression of Aurora-A overrides this cell-cycle block, indicating that Aurora-A is a major effector of the Golgi checkpoint. Our findings provide the basis for further understanding of the signaling pathways that coordinate organelle inheritance and cell duplication.

Golgi partitioning controls mitotic entry through Aurora-A kinase

Barretta ML;Corda D;Colanzi A
2010

Abstract

At the onset of mitosis, the Golgi complex undergoes a multi-step fragmentation process that is required for its correct partitioning into the daughter cells. Inhibition of this Golgi fragmentation results in cell-cycle arrest at the G2 stage, thus suggesting that correct inheritance of the Golgi complex is monitored by a 'Golgi mitotic checkpoint'. However, the molecular basis of this G2 block is not known. Here, we show that the G2-specific Golgi fragmentation stage is concomitant with centrosome recruitment and activation of the mitotic kinase Aurora-A, an essential regulator for entry into mitosis. We show that a block of Golgi partitioning impairs centrosome recruitment and activation of Aurora-A, which results in the G2 block of cell-cycle progression. Overexpression of Aurora-A overrides this cell-cycle block, indicating that Aurora-A is a major effector of the Golgi checkpoint. Our findings provide the basis for further understanding of the signaling pathways that coordinate organelle inheritance and cell duplication.
2010
Istituto di Biochimica delle Proteine - IBP - Sede Napoli
SMALL-MOLECULE INHIBITOR
CELL-CYCLE
PROTEIN-KINASE
DNA-DAMAGE
MAMMALIAN-CELLS
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/126444
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