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PTEN and PI3 Kinase Signaling in the Nervous System

  • Reference work entry
Handbook of Neurochemistry and Molecular Neurobiology

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Abstract

Class I phosphoinositide 3-kinases (PI 3-kinases) synthesise the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate (PIP3) in response to growth factors, neurotransmitters, hormones, cell-cell and cell-matrix contacts. This signal in turn is either removed by the tumour suppressor, phosphatase and tensin homologue deleted on chromosome ten (PTEN), or further metabolised by 5-phosphatases to generate another signal lipid, phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2). PIP3 and PI(3,4)P2 initiate complex signalling cascades through their interactions with highly specific lipid binding domains, most commonly pleckstrin homology (PH) domains, present within a broad range of target proteins. This so-called PI 3-kinase signaling pathway is prominent in both the developing and mature nervous systems of mammals as well as less complex organisms. This review focuses on the mutually antagonistic roles of class I PI 3-kinases and PTEN both of which are required for the development of cell polarity, an essential aspect of neuronal development and morphogenesis as well as neurite extension and navigation. In addition we discuss the importance of this system in diseases of the nervous system. Included in the latter is a survey of the mounting evidence that PI 3-kinase/PTEN signaling may be important in autism spectrum disorders, addictive responses to drugs of abuse, diseases such as diabetes and obesity involving, in part, the central control of metabolism, and several of the most common neurodegenerative diseases.

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Abbreviations

APP:

amyloid precursor protein

ASD:

autistic spectrum disorders

BACE1:

beta site APP-cleaving enzyme

BAD:

Bcl-2 associated death protein

PI3Ks:

phosphoinositide 3-kinases

PI(4,5)P2 :

phosphatidylinositol 4,5-bisphosphate

PIP3 :

phosphatidylinositol 3,4,5-trisphosphate

PKB:

protein kinase B

POMC:

proopiomelanocortin

PTEN:

phosphatase and tensin homologue deleted on chromosome ten

ROS:

reactive oxygen species

TSC:

tuberous sclerosis complex

VTA:

ventral tegmental area

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  1. C. P. Downes
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  2. B. J. Eickholt
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  3. M. L. J. Ashford
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  4. N. R. Leslie
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 10962, 140 Old Orangeburg Road, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Group Director of Neuro-Developmental Disorder Research Group, RIKEN Brain Science Institute, 351-0198, 2-1 Hirosawa Wako-shi, Saitama, Japan

    Katsuhiko Mikoshiba

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Downes, C.P., Eickholt, B.J., Ashford, M.L.J., Leslie, N.R. (2009). PTEN and PI3 Kinase Signaling in the Nervous System. In: Lajtha, A., Mikoshiba, K. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30370-3_13

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