Daam2 phosphorylation by CK2α negatively regulates Wnt activity during white matter development and injury

Chih Yen Wang, Zhongyuan Zuo, Juyeon Jo, Kyoung In Kim, Christine Madamba, Qi Ye, Sung Yun Jung, Hugo J. Bellen, Hyun Kyoung Lee

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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 CK2α, a Wnt/β-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 CK2α-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.

Original languageEnglish
Article numbere2304112120
JournalProceedings of the National Academy of Sciences of the United States of America
Volume120
Issue number35
DOIs
Publication statusPublished - 2023

All Science Journal Classification (ASJC) codes

  • General

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