Editors' ChoiceCell Cycle

Checkpoint Control at the Golgi

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Science's STKE  01 Mar 2005:
Vol. 2005, Issue 273, pp. tw77
DOI: 10.1126/stke.2732005tw77

Mammalian cells employ a checkpoint control mechanism to ensure proper chromosome segregation into daughter cells during mitosis. If the checkpoint pathway senses a defect, cells arrest in metaphase. Organelles, such as the Golgi apparatus, must also disperse equally during cell division. However, it is not clear whether a similar checkpoint pathway exists for sensing organelle integrity during mitosis. Preisinger et al. examined the link between Golgi morphology and cell cycle control and identified a potential signaling pathway to regulate entry into mitosis. GRASP65, a structural component of Golgi membranes, is required for Golgi fragmentation prior to entry into mitosis. The authors determined that the C terminus of GRASP65 is phosphorylated primarily by the mitotic kinase Cdk1-cyclin B. GRASP65 was phosphorylated to a lesser extent by polo-like kinase 1 (Plk1), an enzyme required for normal mitotic spindle function. Phosphorylation of Golgi-associated GRASP65 on the Cdk1-cyclin B consensus sites was visualized in normal rat kidney (NRK) cells by immunofluorescence and correlated with entry into mitosis. Plk1 was detected in a complex with GRASP65 and the Golgi protein GM130 in mitotic cell extracts, but only if GRASP65 was phosphorylated by Cdk1-cyclin B, suggesting that the mitotic kinase creates docking sites on GRASP65 for Plk1. When cells were depleted of Plk1 by RNA interference, mitotic fragmentation of the Golgi into clusters was decreased. Overexpression of the GRASP65 C terminus in NRK cells delayed, rather than arrested, entry into mitosis. However, cells expressing a GRASP65 C terminus harboring a mutant that cannot bind Plk passed through mitosis normally. Because spindle formation and chromosome condensation appeared normal in the presence of the mutant C terminus, passage through mitosis may depend largely on the influence of GRASP65-associated Plk1 on the Golgi. Golgi-associated Plk1 may act on other substrates important for sensing and ensuring appropriate Golgi fragmentation before equal partitioning into daughter cells.

C. Preisinger, R. Körner, M. Wind, W. D. Lehmann, R. Kopajtich, F. A. Barr, Plk1 docking to GRASP65 phosphorylated by Cdk1 suggests a mechanism for Golgi checkpoint signaling. EMBO J. 24, 753-765 (2005). [Abstract] [Full Text]

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