Lactacystin-induced apoptosis of cultured mouse cortical neurons is associated with accumulation of PTEN in the detergent-resistant membrane fraction

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]. Implicit in this notion is that PTEN needs to be targeted to the plasma membrane to dephosphorylate PtdI...

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Published in:Cellular and molecular life sciences : CMLS 2004-07, Vol.61 (15), p.1926-1934
Main Authors: Cheung, N. S, Choy, M. S, Halliwell, B, Teo, T. S, Bay, B. H, Lee, A. Y. -W, Qi, R. Z, Koh, V. H, Whiteman, M, Koaye, E. S. -C, Chiu, L. L, Zhu, H. -J, Wong, K. P, Beart, P. M, Cheng, H. -C
Format: Article
Language:English
Subjects:
Accumulation
Acetylcysteine - analogs & derivatives
Acetylcysteine - metabolism
Acetylcysteine - pharmacology
Animals
Apoptosis
Apoptosis - drug effects
Apoptosis - physiology
caspase-3
Cell Membrane - metabolism
Cerebral Cortex - metabolism
Cysteine Endopeptidases
Cysteine Proteinase Inhibitors - pharmacology
Membranes
Mice
Multienzyme Complexes - antagonists & inhibitors
neurons
Neurons - metabolism
phospholipids
Plasma
plasma membrane
Proteasome Endopeptidase Complex
Protein Tyrosine Phosphatases - metabolism
Proteins
proteolysis
PTEN Phosphohydrolase
Tumor Suppressor Proteins - metabolism
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Summary: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]. Implicit in this notion is that PTEN needs to be targeted to the plasma membrane to dephosphorylate PtdIns(3,4,5)P₃. However, the recruitment of PTEN to the plasma membrane is not fully understood. Here, we demonstrate PTEN accumulation in the detergent-insoluble fraction of neuronal cells in response to treatment by the proteasome inhibitor lactacystin. First, lactacystin induces apoptosis and the activation of caspase-3 in cultured cortical neurons. Second, PTEN undergoes proteolysis to form a truncated 50-kDa form that lacks parts of its C-terminal tail. Third, the truncated PTEN is stably associated with the detergent-insoluble fraction in which the plasma membrane marker protein flotillin-1 resides. Taken together, our results suggest that truncation and accumulation of PTEN to the detergent- insoluble membrane fraction are two events associated with the apoptotic signals of the proteasome inhibitor in cortical neurons.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-004-4127-7