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Review ARTICLE

Front. Mol. Neurosci., 01 April 2014 | http://dx.doi.org/10.3389/fnmol.2014.00023

Subcellular targeting and dynamic regulation of PTEN: implications for neuronal cells and neurological disorders

Patricia Kreis1†, George Leondaritis1,2†, Ivo Lieberam1 and Britta J. Eickholt1,2*
  • 1MRC Centre for Developmental Neurobiology, King's College London, London, UK
  • 2Institute of Biochemistry, Charité – Universitätsmedizin Berlin, Berlin, Germany

PTEN is a lipid and protein phosphatase that regulates a diverse range of cellular mechanisms. PTEN is mainly present in the cytosol and transiently associates with the plasma membrane to dephosphorylate PI(3,4,5)P3, thereby antagonizing the PI3-Kinase signaling pathway. Recently, PTEN has been shown to associate also with organelles such as the endoplasmic reticulum (ER), the mitochondria, or the nucleus, and to be secreted outside of the cell. In addition, PTEN dynamically localizes to specialized sub-cellular compartments such as the neuronal growth cone or dendritic spines. The diverse localizations of PTEN imply a tight temporal and spatial regulation, orchestrated by mechanisms such as posttranslational modifications, formation of distinct protein–protein interactions, or the activation/recruitment of PTEN downstream of external cues. The regulation of PTEN function is thus not only important at the enzymatic activity level, but is also associated to its spatial distribution. In this review we will summarize (i) recent findings that highlight mechanisms controlling PTEN movement and sub-cellular localization, and (ii) current understanding of how PTEN localization is achieved by mechanisms controlling posttranslational modification, by association with binding partners and by PTEN structural or activity requirements. Finally, we will discuss the possible roles of compartmentalized PTEN in developing and mature neurons in health and disease.

Keywords: PTEN phosphohydrolase, neuronal morphology, synaptic transmission, membranes, PI3K/AKT/mTOR

Citation: Kreis P, Leondaritis G, Lieberam I and Eickholt BJ (2014) Subcellular targeting and dynamic regulation of PTEN: implications for neuronal cells and neurological disorders. Front. Mol. Neurosci. 7:23. doi: 10.3389/fnmol.2014.00023

Received: 30 January 2014; Accepted: 12 March 2014;
Published online: 01 April 2014.

Edited by:

Bryan Weston Luikart, Geisel School of Medicine at Dartmouth, USA

Reviewed by:

Kirsten Harvey, University College London, UK
Bernhard Lüscher, Pennsylvania State University, USA

Copyright © 2014 Kreis, Leondaritis, Lieberam and Eickholt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Britta J. Eickholt, Institute of Biochemistry, Charité – Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany e-mail: britta.eickholt@charite.de

These authors have contributed equally to this work.