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PTEN is recruited to specific microdomains of the plasma membrane during lactacystin-induced neuronal apoptosis

Citation

Choy, MS and Bay, BH and Cheng, HC and Cheung, NS, PTEN is recruited to specific microdomains of the plasma membrane during lactacystin-induced neuronal apoptosis, Neuroscience Letters: An International Multidisciplinary Journal Devoted to The Rapid Publication of Basic Research in Neurosciences, 405, (1-2) pp. 120-125. ISSN 0304-3940 (2006) [Refereed Article]

DOI: doi:10.1016/j.neulet.2006.06.037

Abstract

The tumor suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10) is a novel phosphatase displaying both protein and lipid phosphatase activities. In the central nervous system, PTEN plays an important role in the regulation of cell growth, differentiation and death. The tumor suppressor function of PTEN is attributed to its phospholipid phosphatase activity that dephosphorylates the plasma membrane phosphatidylinositol-(3,4,5)-triphosphate (PtdIns(3,4,5)P3). Since PTEN is normally localized in the cytosol, it needs to be targeted to the plasma membrane to dephosphorylate PtdIns(3,4,5)P3. We previously demonstrated that lactacystin-induced apoptosis of culture cortical neuron is associated with: (i) cleavage of PTEN (55 kDa) to a 50 kDa truncated form and (ii) accumulation of PTEN and all the truncated PTEN in a detergent-insoluble membrane fraction of the neuronal cells. Herein we demonstrate that a caspase-3 inhibitor suppresses cleavage of PTEN to the 50 kDa truncated form in culture cortical neurons in response to lactacystin treatment. Using immunogold transmission electron microscopy, we examined the distribution of PTEN in plasma membrane sheets stripped from cultured cortical neurons with and without treatment of lactacystin. Our results demonstrate that lactacystin treatment induces accumulation of PTEN to the inner surface of the plasma membrane sheets of the neuronal cells. Taken together, our data suggest that caspase-3-like proteases are involved in the conversion of PTEN to a 50-kDa truncated form and that PTEN and its truncated form accumulate at specific microdomains of the plasma membrane in neuronal cells undergoing apoptosis.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Cheung, NS (Dr Nam Cheung)
ID Code:61623
Year Published:2006
Web of Science® Times Cited:9
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-03-04
Last Modified:2010-05-03
Downloads:0

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