Letter abstract


Nature Cell Biology 11, 1191 - 1196 (2009)
Published online: 20 September 2009 | Corrected online: 5 October 2009 | doi:10.1038/ncb1961



There is an Erratum (November 2009) associated with this Letter.

MyosinV controls PTEN function and neuronal cell size

Michiel T. van Diepen1, Maddy Parsons2, C. Peter Downes3, Nicholas R. Leslie3, Robert Hindges1 & Britta J Eickholt1

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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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  1. MRC Centre for Developmental Neurobiology, New Hunt's House, King's College London, London SE1 1UL, UK.
  2. The Randall Division of Cell and Molecular Biophysics, New Hunt's House, King's College London, London SE1 1UL, UK.
  3. Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee, Scotland, DD1 5EH, UK.

Correspondence to: Britta J Eickholt1 e-mail: britta.J.eickholt@kcl.ac.uk.

* 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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