| First Author | Wang CY | Year | 2023 |
| Journal | Proc Natl Acad Sci U S A | Volume | 120 |
| Issue | 35 | Pages | e2304112120 |
| PubMed ID | 37607236 | Mgi Jnum | J:341055 |
| Mgi Id | MGI:7528680 | Doi | 10.1073/pnas.2304112120 |
| Citation | Wang CY, et al. (2023) Daam2 phosphorylation by CK2alpha negatively regulates Wnt activity during white matter development and injury. Proc Natl Acad Sci U S A 120(35):e2304112120 |
| abstractText | Wnt signaling plays an essential role in developmental and regenerative myelination in the central nervous system. The Wnt signaling pathway is composed of multiple regulatory layers; thus, how these processes are coordinated to orchestrate oligodendrocyte (OL) development remains unclear. Here, we show CK2alpha, a Wnt/beta-catenin signaling Ser/Thr kinase, phosphorylates Daam2, inhibiting its function and Wnt activity during OL development. Intriguingly, we found Daam2 phosphorylation differentially impacts distinct stages of OL development, accelerating early differentiation followed by decelerating maturation and myelination. Application toward white matter injury revealed CK2alpha-mediated Daam2 phosphorylation plays a protective role for developmental and behavioral recovery after neonatal hypoxia, while promoting myelin repair following adult demyelination. Together, our findings identify a unique regulatory node in the Wnt pathway that regulates OL development via protein phosphorylation-induced signaling complex instability and highlights a new biological mechanism for myelin restoration. |
