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MyosinV controls PTEN function and neuronal cell size

Nature Cell Biology volume 11, pages 1191–1196 (2009)Cite this article

An Erratum to this article was published on 01 November 2009

This article has been updated

Abstract

The tumour suppressor PTEN can inhibit cell proliferation and migration as well as control cell growth, in different cell types1. PTEN functions predominately as a lipid phosphatase, converting PtdIns(3,4,5)P3 to PtdIns(4,5)P2, thereby antagonizing PI(3)K (phosphoinositide 3-kinase) and its established downstream effector pathways2. However, much is unclear concerning the mechanisms that regulate PTEN movement to the cell membrane, which is necessary for its activity towards PtdIns(3,4,5)P3 (Refs 3, 4, 5). Here we show a requirement for functional motor proteins in the control of PI3K signalling, involving a previously unknown association between PTEN and myosinV. FRET (Förster resonance energy transfer) measurements revealed that PTEN interacts directly with myosinV, which is dependent on PTEN phosphorylation mediated by CK2 and/or GSK3. Inactivation of myosinV-transport function in neurons increased cell size, which, in line with known attributes of PTEN-loss6,7, required PI(3)K and mTor. Our data demonstrate a myosin-based transport mechanism that regulates PTEN function, providing new insights into the signalling networks regulating cell growth.

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Figure 1: Identification and characterization of the PTEN:myosinVa interaction.
Figure 2: MyosinV regulates neuronal soma size through PI3K signalling.
Figure 3: The PTEN:myosinV interaction is mediated by a positively charged region in myosinVa.
Figure 4: Neuronal soma size is controlled by GSK3 and CK2 upstream of PTEN and myosinV.

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  • 05 October 2009

    In the version of this article initially published, the directions of the horizontal arrows in Fig. 4b were reversed. This error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

This work was funded by the Biotechnology and Biological Science Research Council to B.J.E. (BB/C514307/1), an MRC program grant to C.P.D. (G9403619). M.P. is a Royal Society University Research Fellow. We thank J. Hammer III for providing the myosinVa cDNA, C. Sutherland for the GSK3 inhibitor CT99021, E. Blanc for help with statistical analyses and F. Gertler for comments on the manuscript.

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Authors and Affiliations

  1. MRC Centre for Developmental Neurobiology, New Hunt's House, King's College London, SE1 1UL, London, UK

    Michiel T. van Diepen, Robert Hindges & Britta J Eickholt

  2. The Randall Division of Cell and Molecular Biophysics, New Hunt's House, King's College London, SE1 1UL, London, UK

    Maddy Parsons

  3. Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, UK

    C. Peter Downes & Nicholas R. Leslie

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  1. Michiel T. van Diepen
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Contributions

All authors designed experiments; M.v.D., M.P., R.H. and B.J.E. performed research and B.J.E. wrote the manuscript.

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Correspondence to Britta J Eickholt.

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van Diepen, M., Parsons, M., Downes, C. et al. MyosinV controls PTEN function and neuronal cell size. Nat Cell Biol 11, 1191–1196 (2009). https://doi.org/10.1038/ncb1961

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