이현경 (Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute)

한빛사논문

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Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute

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Proc. Natl. Acad. Sci. USA, 2023 Aug 29;120(35):e2304112120 | https://doi.org/10.1073/pnas.2304112120 Daam2 phosphorylation by CK2α negatively regulates Wnt activity during white matter development and injury

Chih-Yen Wang^a,b,c, Zhongyuan Zuo^b,d, Juyeon Jo^a,b, Kyoung In Kim^a,b, Christine Madamba^b,e, Qi Ye^a,b, Sung Yun Jung^f, Hugo J. Bellen^b,d,g, and Hyun Kyoung Lee^a,b,e,g,1

^aDepartment of Pediatrics, Section of Neurology, Baylor College of Medicine, Houston, TX 77030
^bJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030
^cDepartment of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan 70101, Taiwan
^dDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030
^eCancer and Cell Biology Program, Baylor College of Medicine, Houston, TX 77030
^fDepartment of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030
^gDepartment of Neuroscience, Baylor College of Medicine, Houston, TX 77030

¹To whom correspondence may be addressed

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.

논문정보

형식Research article
게재일2023년 08월 (BRIC 등록일 2023-08-23)
연구진국외 연구진
분야 의약학 > 신경의학

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