Subcellular targeting and dynamic regulation of PTEN: implications for neuronal cells and neurological disorders
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 show...
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Frontiers Media S.A.
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978343/ |
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pubmed-39783432014-04-17 Subcellular targeting and dynamic regulation of PTEN: implications for neuronal cells and neurological disorders Kreis, Patricia Leondaritis, George Lieberam, Ivo Eickholt, Britta J. Neuroscience 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. Frontiers Media S.A. 2014-04-01 /pmc/articles/PMC3978343/ /pubmed/24744697 http://dx.doi.org/10.3389/fnmol.2014.00023 Text en Copyright © 2014 Kreis, Leondaritis, Lieberam and Eickholt. http://creativecommons.org/licenses/by/3.0/ 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. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Kreis, Patricia Leondaritis, George Lieberam, Ivo Eickholt, Britta J. |
| spellingShingle |
Kreis, Patricia Leondaritis, George Lieberam, Ivo Eickholt, Britta J. Subcellular targeting and dynamic regulation of PTEN: implications for neuronal cells and neurological disorders |
| author_facet |
Kreis, Patricia Leondaritis, George Lieberam, Ivo Eickholt, Britta J. |
| author_sort |
Kreis, Patricia |
| title |
Subcellular targeting and dynamic regulation of PTEN: implications for neuronal cells and neurological disorders |
| title_short |
Subcellular targeting and dynamic regulation of PTEN: implications for neuronal cells and neurological disorders |
| title_full |
Subcellular targeting and dynamic regulation of PTEN: implications for neuronal cells and neurological disorders |
| title_fullStr |
Subcellular targeting and dynamic regulation of PTEN: implications for neuronal cells and neurological disorders |
| title_full_unstemmed |
Subcellular targeting and dynamic regulation of PTEN: implications for neuronal cells and neurological disorders |
| title_sort |
subcellular targeting and dynamic regulation of pten: implications for neuronal cells and neurological disorders |
| description |
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. |
| publisher |
Frontiers Media S.A. |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978343/ |
| _version_ |
1612075103970918400 |