Prader-Willi syndrome protein necdin regulates the nucleocytoplasmic distribution and dopaminergic neuron development
Abstract Dopamine (DA) plays important roles in various behaviors, including learning and motivation. Recently, THOC5 was identified as an important regulator in the development of dopaminergic neurons. However, how THOC5 is regulated has not been explored. In this study, we found an interaction bet...
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| Format: | Article |
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Nature Portfolio
2024-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-76981-y |
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| author | Xin Li Yichun Zhang Ying Hu Xiangrong Tang Zishan Gong Ren-bin Lu Jia-da Li |
| author_facet | Xin Li Yichun Zhang Ying Hu Xiangrong Tang Zishan Gong Ren-bin Lu Jia-da Li |
| author_sort | Xin Li |
| collection | DOAJ |
| description | Abstract Dopamine (DA) plays important roles in various behaviors, including learning and motivation. Recently, THOC5 was identified as an important regulator in the development of dopaminergic neurons. However, how THOC5 is regulated has not been explored. In this study, we found an interaction between THOC5 and necdin, which is encoded by a gene located in the chromosome deletion region of Prader-Willi syndrome (PWS), by using a yeast two-hybrid assay. Necdin affects the mRNA export function of THOC5 by regulating its nucleocytoplasmic localization. As a result, the expression of a few DA neuronal development-related genes, such as Mef2c, Lef1 and Prkcg, is altered in necdin-deficient mice. We also found neurodegeneration of dopaminergic neurons and an increase of glial cells in necdin-deficient mice, which may underlie the dyspraxia behaviors in these mice. Our results thus identified necdin as a novel regulator for THOC5, which may underlie, at least partly, the abnormal DA neuron development in necdin-deficient mice. |
| format | Article |
| id | doaj-art-80d985275468408487027cb926280ed3 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-80d985275468408487027cb926280ed32025-01-05T12:24:39ZengNature PortfolioScientific Reports2045-23222024-12-0114111010.1038/s41598-024-76981-yPrader-Willi syndrome protein necdin regulates the nucleocytoplasmic distribution and dopaminergic neuron developmentXin Li0Yichun Zhang1Ying Hu2Xiangrong Tang3Zishan Gong4Ren-bin Lu5Jia-da Li6Center for Medical Genetics, School of Life Sciences, Central South UniversityFurong Laboratory, Department of Anaesthesiology, Xiangya Hospital, Central South UniversityFurong Laboratory, Department of Anaesthesiology, Xiangya Hospital, Central South UniversityCenter for Reproductive Medicine, Women and Children’s Hospital of Chongqing Medical UniversityFurong Laboratory, Department of Anaesthesiology, Xiangya Hospital, Central South UniversityCenter for Medical Genetics, School of Life Sciences, Central South UniversityCenter for Medical Genetics, School of Life Sciences, Central South UniversityAbstract Dopamine (DA) plays important roles in various behaviors, including learning and motivation. Recently, THOC5 was identified as an important regulator in the development of dopaminergic neurons. However, how THOC5 is regulated has not been explored. In this study, we found an interaction between THOC5 and necdin, which is encoded by a gene located in the chromosome deletion region of Prader-Willi syndrome (PWS), by using a yeast two-hybrid assay. Necdin affects the mRNA export function of THOC5 by regulating its nucleocytoplasmic localization. As a result, the expression of a few DA neuronal development-related genes, such as Mef2c, Lef1 and Prkcg, is altered in necdin-deficient mice. We also found neurodegeneration of dopaminergic neurons and an increase of glial cells in necdin-deficient mice, which may underlie the dyspraxia behaviors in these mice. Our results thus identified necdin as a novel regulator for THOC5, which may underlie, at least partly, the abnormal DA neuron development in necdin-deficient mice.https://doi.org/10.1038/s41598-024-76981-y |
| spellingShingle | Xin Li Yichun Zhang Ying Hu Xiangrong Tang Zishan Gong Ren-bin Lu Jia-da Li Prader-Willi syndrome protein necdin regulates the nucleocytoplasmic distribution and dopaminergic neuron development Scientific Reports |
| title | Prader-Willi syndrome protein necdin regulates the nucleocytoplasmic distribution and dopaminergic neuron development |
| title_full | Prader-Willi syndrome protein necdin regulates the nucleocytoplasmic distribution and dopaminergic neuron development |
| title_fullStr | Prader-Willi syndrome protein necdin regulates the nucleocytoplasmic distribution and dopaminergic neuron development |
| title_full_unstemmed | Prader-Willi syndrome protein necdin regulates the nucleocytoplasmic distribution and dopaminergic neuron development |
| title_short | Prader-Willi syndrome protein necdin regulates the nucleocytoplasmic distribution and dopaminergic neuron development |
| title_sort | prader willi syndrome protein necdin regulates the nucleocytoplasmic distribution and dopaminergic neuron development |
| url | https://doi.org/10.1038/s41598-024-76981-y |
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