| First Author | Nakamura K | Year | 2012 |
| Journal | Mol Cell Biol | Volume | 32 |
| Issue | 15 | Pages | 2966-78 |
| PubMed ID | 22645310 | Mgi Jnum | J:186644 |
| Mgi Id | MGI:5432836 | Doi | 10.1128/MCB.05688-11 |
| Citation | Nakamura K, et al. (2012) Prolyl Isomerase Pin1 Regulates Neuronal Differentiation via beta-Catenin. Mol Cell Biol 32(15):2966-78 |
| abstractText | The Wnt/beta-catenin pathway promotes proliferation of neural progenitor cells (NPCs) at early stages and induces neuronal differentiation from NPCs at late stages, but the molecular mechanisms that control this stage-specific response are unclear. Pin1 is a prolyl isomerase that regulates cell signaling uniquely by controlling protein conformation after phosphorylation, but its role in neuronal differentiation is not known. Here we found that whereas Pin1 depletion suppresses neuronal differentiation, Pin1 overexpression enhances it, without any effects on gliogenesis from NPCs in vitro. Consequently, Pin1-null mice have significantly fewer upper layer neurons in the motor cortex and severely impaired motor activity during the neonatal stage. A proteomic approach identified beta-catenin as a major substrate for Pin1 in NPCs, in which Pin1 stabilizes beta-catenin. As a result, Pin1 knockout leads to reduced beta-catenin during differentiation but not proliferation of NPCs in developing brains. Importantly, defective neuronal differentiation in Pin1 knockout NPCs is fully rescued in vitro by overexpression of beta-catenin but not a beta-catenin mutant that fails to act as a Pin1 substrate. These results show that Pin1 is a novel regulator of NPC differentiation by acting on beta-catenin and provides a new postphosphorylation signaling mechanism to regulate developmental stage-specific functioning of beta-catenin signaling in neuronal differentiation. |
