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Golgi partitioning controls mitotic entry through Aurora-A kinase.

Persico A, Cervigni RI, Barretta ML, Corda D, Colanzi A - Mol. Biol. Cell (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Chieti, Italy.

ABSTRACT
At the onset of mitosis, the Golgi complex undergoes a multistep 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, 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.

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The block of severing of the Golgi ribbon during G2 inhibits the recruitment and activation of Aur-A at the centrosome trough a novel mechanism. (A) In mammalian cells, the Golgi complex is organized as a continuous membranous system composed of stacks interconnected by tubules, a structure known as the Golgi ribbon (ribbon). During the G2 phase of the cell cycle, the severing of the Golgi ribbon into its constituent stacks (stacks) is a fragmentation step that is essential for mitotic entrance and is concomitant with the initial recruitment and activation of Aur-A kinase at the centrosomes (CE). A block in Golgi fragmentation (X) inhibits Aur-A recruitment and activation at the centrosome, and this in turn impairs the first activation of cycB-Cdk1 at the centrosome. The Golgi-dependent G2 block is not mediated by known Aur-A activators (i.e., Pak1), and neither it is indirectly mediated or Plk1 and the cycB–Cdk1 complex. (B) The Golgi-dependent G2 block is not regulated by known G2 checkpoint mediators (e.g., : Chk1 or p38), and neither it is mediated by Golgi-localized cell cycle regulators (e.g., : Myt-1), which act downstream the Golgi checkpoint. (C) At the onset of mitosis the kinases Aur-A, Plk1 and cycB-Cdk1 become functionally connected by a positive feedback loop, leading to irreversible progression into mitosis.
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Figure 10: The block of severing of the Golgi ribbon during G2 inhibits the recruitment and activation of Aur-A at the centrosome trough a novel mechanism. (A) In mammalian cells, the Golgi complex is organized as a continuous membranous system composed of stacks interconnected by tubules, a structure known as the Golgi ribbon (ribbon). During the G2 phase of the cell cycle, the severing of the Golgi ribbon into its constituent stacks (stacks) is a fragmentation step that is essential for mitotic entrance and is concomitant with the initial recruitment and activation of Aur-A kinase at the centrosomes (CE). A block in Golgi fragmentation (X) inhibits Aur-A recruitment and activation at the centrosome, and this in turn impairs the first activation of cycB-Cdk1 at the centrosome. The Golgi-dependent G2 block is not mediated by known Aur-A activators (i.e., Pak1), and neither it is indirectly mediated or Plk1 and the cycB–Cdk1 complex. (B) The Golgi-dependent G2 block is not regulated by known G2 checkpoint mediators (e.g., : Chk1 or p38), and neither it is mediated by Golgi-localized cell cycle regulators (e.g., : Myt-1), which act downstream the Golgi checkpoint. (C) At the onset of mitosis the kinases Aur-A, Plk1 and cycB-Cdk1 become functionally connected by a positive feedback loop, leading to irreversible progression into mitosis.

Mentions: Thus, the Golgi checkpoint cannot be overridden by treatments that can bypass the known G2 checkpoints. This suggests further that Aur-A recruitment to and activation at the centrosome is connected with the partitioning of the Golgi ribbon through a novel signaling mechanism (Figure 10). Moreover, these last data again indicate that centrosome located and activated Aur-A is a cell cycle component that functions as the major effector of the Golgi checkpoint.


Golgi partitioning controls mitotic entry through Aurora-A kinase.

Persico A, Cervigni RI, Barretta ML, Corda D, Colanzi A - Mol. Biol. Cell (2010)

The block of severing of the Golgi ribbon during G2 inhibits the recruitment and activation of Aur-A at the centrosome trough a novel mechanism. (A) In mammalian cells, the Golgi complex is organized as a continuous membranous system composed of stacks interconnected by tubules, a structure known as the Golgi ribbon (ribbon). During the G2 phase of the cell cycle, the severing of the Golgi ribbon into its constituent stacks (stacks) is a fragmentation step that is essential for mitotic entrance and is concomitant with the initial recruitment and activation of Aur-A kinase at the centrosomes (CE). A block in Golgi fragmentation (X) inhibits Aur-A recruitment and activation at the centrosome, and this in turn impairs the first activation of cycB-Cdk1 at the centrosome. The Golgi-dependent G2 block is not mediated by known Aur-A activators (i.e., Pak1), and neither it is indirectly mediated or Plk1 and the cycB–Cdk1 complex. (B) The Golgi-dependent G2 block is not regulated by known G2 checkpoint mediators (e.g., : Chk1 or p38), and neither it is mediated by Golgi-localized cell cycle regulators (e.g., : Myt-1), which act downstream the Golgi checkpoint. (C) At the onset of mitosis the kinases Aur-A, Plk1 and cycB-Cdk1 become functionally connected by a positive feedback loop, leading to irreversible progression into mitosis.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2965687&req=5

Figure 10: The block of severing of the Golgi ribbon during G2 inhibits the recruitment and activation of Aur-A at the centrosome trough a novel mechanism. (A) In mammalian cells, the Golgi complex is organized as a continuous membranous system composed of stacks interconnected by tubules, a structure known as the Golgi ribbon (ribbon). During the G2 phase of the cell cycle, the severing of the Golgi ribbon into its constituent stacks (stacks) is a fragmentation step that is essential for mitotic entrance and is concomitant with the initial recruitment and activation of Aur-A kinase at the centrosomes (CE). A block in Golgi fragmentation (X) inhibits Aur-A recruitment and activation at the centrosome, and this in turn impairs the first activation of cycB-Cdk1 at the centrosome. The Golgi-dependent G2 block is not mediated by known Aur-A activators (i.e., Pak1), and neither it is indirectly mediated or Plk1 and the cycB–Cdk1 complex. (B) The Golgi-dependent G2 block is not regulated by known G2 checkpoint mediators (e.g., : Chk1 or p38), and neither it is mediated by Golgi-localized cell cycle regulators (e.g., : Myt-1), which act downstream the Golgi checkpoint. (C) At the onset of mitosis the kinases Aur-A, Plk1 and cycB-Cdk1 become functionally connected by a positive feedback loop, leading to irreversible progression into mitosis.
Mentions: Thus, the Golgi checkpoint cannot be overridden by treatments that can bypass the known G2 checkpoints. This suggests further that Aur-A recruitment to and activation at the centrosome is connected with the partitioning of the Golgi ribbon through a novel signaling mechanism (Figure 10). Moreover, these last data again indicate that centrosome located and activated Aur-A is a cell cycle component that functions as the major effector of the Golgi checkpoint.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Chieti, Italy.

ABSTRACT
At the onset of mitosis, the Golgi complex undergoes a multistep 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, 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.

Show MeSH
Related in: MedlinePlus