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Metabolic-energy-dependent movement of PML bodies within the mammalian cell nucleus

Abstract

Promyelocytic leukaemia (PML) nuclear bodies are present in most mammalian cell nuclei. PML bodies are disrupted by PML retinoic acid receptor alpha (RARα) oncoproteins in acute promyelocytic leukaemia. These bodies contain numerous proteins, including Sp100, SUMO-1, HAUSP(USP7), CBP and BLM, and they have been implicated in aspects of transcriptional regulation or as nuclear storage depots. Here, we show that three classes of PML nuclear bodies can be distinguished, on the basis of their dynamic properties in living cells. One class of PML bodies is particularly noteworthy in that it moves by a metabolic-energy-dependent mechanism. This represents the first example of metabolic-energy-dependent transport of a nuclear body within the mammalian cell nucleus.

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Figure 1: Characterization of the EYFP–Sp100 fusion protein.
Figure 2: PML bodies can be classified into three groups on the basis of their nuclear dynamics.
Figure 3: Tracking of PML bodies in time and space.
Figure 4: PML bodies can move in quasi-linear trajectories.
Figure 5: A subset of PML bodies move by a metabolic-energy-dependent mechanism.
Figure 6: The myosin inhibitor BDM reduced the velocity of rapidly moving PML bodies.

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Acknowledgements

We would like to acknowledge members of the Spector laboratory and E. Heard for helpful discussions and suggestions. The GFP–Sp100 plasmid was kindly provided by G. Maul, Wistar Institute, Philadelphia, PA. M.M. is a George A. and Marjorie H. Anderson Fellow of the Watson School of Biological Sciences. R.E. acknowledges the support of the German Federal Ministry of Education and Research (BMBF) through a BioFuture grant. This work was supported by grant 498100 to D.L.S. from the National Institutes of Health / National Institute of General Medical Sciences.

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Correspondence to David L. Spector.

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Supplementary information

Movie 1

Dynamics of PML bodies in BHK cells (see paper for detailed explanations). (MOV 901 kb)

Movie 2

Effects of ATP depletion on PML body dynamics (see paper for detailed explanations). (MOV 5255 kb)

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Muratani, M., Gerlich, D., Janicki, S. et al. Metabolic-energy-dependent movement of PML bodies within the mammalian cell nucleus. Nat Cell Biol 4, 106–110 (2002). https://doi.org/10.1038/ncb740

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