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The Journal of Neuroscience, February 15, 2000, 20(4):1404-1413
A Role for Nuclear PTEN in Neuronal Differentiation
Mahesh B.
Lachyankar1,
Nazneen
Sultana1,
Christopher M.
Schonhoff2,
Prasenjit
Mitra1,
Wojciech
Poluha1,
Stephen
Lambert3,
Peter J.
Quesenberry4,
N. Scott
Litofsky5,
Lawrence D.
Recht6,
Roya
Nabi7,
Susan J.
Miller8,
Shinji
Ohta8,
Benjamin G.
Neel8, and
Alonzo H.
Ross1
Departments of 1 Pharmacology and Molecular Toxicology,
2 Biochemistry and Molecular Biology, 3 Cell
Biology, 4 Medicine (Cancer Center), 5 Surgery,
and 6 Neurology, University of Massachusetts Medical
School, Worcester, Massachusetts 01655, 7 Department
of Biology and Biotechnology, Worcester Polytechnic Institute,
Worcester, Massachusetts 01609, and 8 Cancer Biology
Program, Division of Hematology-Oncology, Department of Medicine, Beth
Israel-Deaconess Medical Center, Boston, Massachusetts 02215
Mutations of phosphatase and tensin homolog deleted on chromosome
10 (PTEN), a protein and lipid phosphatase, have been associated with gliomas, macrocephaly, and mental deficiencies. We have assessed PTEN's role in the nervous system and find that PTEN is expressed in
mouse brain late in development, starting at approximately postnatal
day 0. In adult brain, PTEN is preferentially expressed in
neurons and is especially evident in Purkinje neurons, olfactory mitral
neurons, and large pyramidal neurons. To analyze the function of PTEN
in neuronal differentiation, we used two well established model
systems pheochromocytoma cells and cultured CNS stem cells. PTEN is
expressed during neurotrophin-induced differentiation and is detected
in both the nucleus and cytoplasm. Suppression of PTEN levels with
antisense oligonucleotides does not block initiation of neuronal
differentiation. Instead, PTEN antisense leads to death of the
resulting, immature neurons, probably during neurite extension. In
contrast, PTEN is not required for astrocytic differentiation. These
observations indicate that PTEN acts at multiple sites in the cell,
regulating the transition of differentiating neuroblasts to postmitotic neurons.
Key words:
phosphatase; phosphatidylinositol phosphate; nerve growth
factor; PC12 cells; stem cells; brain-derived neurotrophic factor; neurite extension
Copyright © 2000 Society for Neuroscience 0270-6474/00/2041404-10$05.00/0
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67(22):
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177(5):
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281(36):
26562 - 26568.
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H. Tsuruta, H. Kishimoto, T. Sasaki, Y. Horie, M. Natsui, Y. Shibata, K. Hamada, N. Yajima, K. Kawahara, M. Sasaki, et al.
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66(17):
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119(Pt 5):
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65(10):
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64(21):
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101(10):
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45(1):
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|
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|
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|
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|
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278(33):
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|
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|
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277(43):
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|
|
|
|
|
|
|
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July 1, 2002;
4(3):
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[Abstract]
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|
|
|
|
|
|
|
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August 1, 2001;
7(4):
278 - 281.
[Abstract]
[PDF]
|
|
|
|
|
|
|
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158(6):
2097 - 2106.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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157(4):
1097 - 1103.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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|
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