| First Author | Tan M | Year | 2013 |
| Journal | J Neurochem | Volume | 125 |
| Issue | 5 | Pages | 685-97 |
| PubMed ID | 23470087 | Mgi Jnum | J:197942 |
| Mgi Id | MGI:5494923 | Doi | 10.1111/jnc.12230 |
| Citation | Tan M, et al. (2013) GSK-3alpha/beta-mediated phosphorylation of CRMP-2 regulates activity-dependent dendritic growth. J Neurochem 125(5):685-97 |
| abstractText | Neuronal activity shapes the dendritic arbour; however, most of the molecular players in this process remain to be identified. We observed that depolarization-induced neuronal activity causes an increase in the phosphorylation of glycogen synthase kinase-3 (GSK-3)alpha/beta on Ser21/9 in cerebellar granule neurons. Using several approaches, including gene knockdown and GSK-3alpha/beta(S21A/S21A/S9A/S9A) double knockin mice, we demonstrated that both GSK-3beta and GSK-3alpha mediate activity-dependent dendritic growth and that Ser21/9 phosphorylation of GSK-3alpha/beta plays an important role in this process. Collapsin response mediator protein-2 (CRMP-2), which is crucial for axon development, is phosphorylated at Thr514 and inactivated by GSK-3. We found CRMP-2 was located mainly in the dendrites of cerebellar granule neurons, in contrast to the axonal distribution in hippocampal neurons. Over-expression of CRMP-2 promoted and knockdown of CRMP-2 impaired dendritic growth, suggesting that CRMP-2 is necessary and sufficient for activity-dependent dendritic development. Furthermore, silencing CRMP-2 completely blocked the dendritic growth-promoting effects of GSK-3 knockdown, and expression of Thr514 nonphosphorylated form of CRMP-2 counteracted the inhibitory effect of constitutively active GSK-3. This data indicate that CRMP-2 functions downstream of GSK-3. Together, these findings identify a novel GSK-3/CRMP-2 pathway that connects neuronal activity to dendritic growth. |
