The protein phosphatase activity of PTEN is essential for regulating neural stem cell differentiation
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...
Saved in:
Published in | Molecular brain Vol. 8; no. 1; p. 26 |
---|---|
Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
BioMed Central Ltd
18.04.2015
BioMed Central |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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.
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.
Our data indicate that the protein phosphatase activity of PTEN is critical for regulating differentiation of NSCs during cortical development. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1756-6606 1756-6606 |
DOI: | 10.1186/s13041-015-0114-1 |