한빛사논문
- 조회620
Inwoo Hwang1,2, Byeong-Seong Kim1,2, Hyo Rim Ko1, Seongbong Cho1, Ho Yun Lee3, Sung-Woo Cho4, Dongryeol Ryu1, Sungbo Shim5 and Jee-Yin Ahn1,2,6,*
1Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, South Korea. 2Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, South Korea. 3Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 4Department of Biochemistry and Molecular Biology, University of Ulsan, College of Medicine, Seoul 05505, South Korea. 5Department of Biochemistry, Chungbuk National University, Cheongju, South Korea. 6Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, South Korea.
*Corresponding author.
Abstract
Cerebellar deficits with Purkinje cell (PCs) loss are observed in several neurologic disorders. However, the underlying mechanisms as to how the cerebellum is affected during development remain unclear. Here we demonstrated that specific inactivation of murine Ebp1 in the central nervous system causes a profound neuropathology characterized by reduced cerebellar volume and PCs loss with abnormal dendritic development, leading to phenotypes including motor defects and schizophrenia (SZ)-like behaviors. Loss of Ebp1 leads to untimely gene expression of Fbxw7, an E3 ubiquitin ligase, resulting in aberrant protein degradation of PTF1A, thereby eliciting cerebellar defects. Reinstatement of Ebp1, but not the Ebp1-E183Ter mutant found in SZ patients, reconstituted cerebellar architecture with increased PCs numbers and improved behavioral phenotypes. Thus, our findings indicate a crucial role for EBP1 in cerebellar development, and define a molecular basis for the cerebellar contribution to neurologic disorders such as SZ.
논문정보
- Research article
- 2022년 02월 (BRIC 등록일 2022-03-14)
- 국내 연구진
- 의약학 > 신경의학
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