The protein phosphatase activity of PTEN is essential for regulating neural stem cell differentiation.
BACKGROUND
The tumor suppressor gene Phosphatase and tensin homolog (PTEN) is highly expressed in neural progenitor cells (NPCs) and plays an important role in development of the central nervous system. As a dual-specificity phosphatase, the loss of PTEN phosphatase activity has been linked to various diseases.


RESULTS
Here we report that the protein phosphatase activity of Pten is critical for regulating differentiation of neural progenitor cells. First we found that deletion of Pten promotes neuronal differentiation. To determine whether the protein or lipid phosphatase activity is required for regulating neuronal differentiation, we generated phosphatase domain-specific Pten mutations. Interestingly, only expression of protein phosphatase-deficient mutant Y138L could mimic the effect of knocking down Pten, suggesting the protein phosphatase of Pten is critical for regulating NPC differentiation. Importantly, we showed that the wild-type and lipid phosphatase mutant (G129E) forms of Pten are able to rescue neuronal differentiation in Pten knockout NPCs, but mutants containing protein phosphatase mutant cannot. We further found that Pten-dependent dephosphorylation of CREB is critical for neuronal differentiation.


CONCLUSIONS
Our data indicate that the protein phosphatase activity of PTEN is critical for regulating differentiation of NSCs during cortical development.
Departments of Neonatology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. jlv13@fudan.edu.cn.
Jingwen
J
Lyu
Departments of Neonatology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. 522528894@qq.com.
Xiuya
X
Yu
Institute of Neuroscience, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. ljhe@ion.ac.cn.
Lingjie
L
He
Institute of Neuroscience, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. tlcheng@ion.ac.cn.
Tianlin
T
Cheng
Departments of Neonatology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. zhoujingjing666666@yeah.net.
Jingjing
J
Zhou
Institute of Neuroscience, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. ccheng@ion.ac.cn.
Cheng
C
Cheng
Institute of Neuroscience, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. zfchen@ion.ac.cn.
Zhifang
Z
Chen
Departments of Neonatology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. gqchengcm@sina.com.cn.
Guoqiang
G
Cheng
Institute of Neuroscience, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. zqiu@ion.ac.cn.
Zilong
Z
Qiu
Departments of Neonatology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. zwhchfu@126.com.
Wenhao
W
Zhou
D000818:Animals; D002454:Cell Differentiation; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004789:Enzyme Activation; D017353:Gene Deletion; D055785:Gene Knockdown Techniques; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000201:enzymology*; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference
D017362:Cyclic AMP Response Element-Binding Protein; D050505:Mutant Proteins; D051059:PTEN Phosphohydrolase