دورية أكاديمية
PINK1-mediated Drp1S616 phosphorylation modulates synaptic development and plasticity via promoting mitochondrial fission
| العنوان: | PINK1-mediated Drp1S616 phosphorylation modulates synaptic development and plasticity via promoting mitochondrial fission |
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| المؤلفون: | Qingtao Gao, Runyi Tian, Hailong Han, Jesse Slone, Caifang Wang, Xiao Ke, Tongmei Zhang, Xiangyu Li, Yuhong He, Panlin Liao, Fang Wang, Ye Chen, Shiqing Fu, Kexuan Zhang, Fangfang Zeng, Yingxuan Yang, Zhuo Li, Jieqiong Tan, Jiada Li, Youming Lu, Taosheng Huang, Zhonghua Hu, Zhuohua Zhang |
| المصدر: | Signal Transduction and Targeted Therapy, Vol 7, Iss 1, Pp 1-16 (2022) |
| بيانات النشر: | Nature Publishing Group, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine LCC:Biology (General) |
| مصطلحات موضوعية: | Medicine, Biology (General), QH301-705.5 |
| الوصف: | Abstract Dynamic change of mitochondrial morphology and distribution along neuronal branches are essential for neural circuitry formation and synaptic efficacy. However, the underlying mechanism remains elusive. We show here that Pink1 knockout (KO) mice display defective dendritic spine maturation, reduced axonal synaptic vesicles, abnormal synaptic connection, and attenuated long-term synaptic potentiation (LTP). Drp1 activation via S616 phosphorylation rescues deficits of spine maturation in Pink1 KO neurons. Notably, mice harboring a knockin (KI) phosphor-null Drp1 S616A recapitulate spine immaturity and synaptic abnormality identified in Pink1 KO mice. Chemical LTP (cLTP) induces Drp1S616 phosphorylation in a PINK1-dependent manner. Moreover, phosphor-mimetic Drp1S616D restores reduced dendritic spine localization of mitochondria in Pink1 KO neurons. Together, this study provides the first in vivo evidence of functional regulation of Drp1 by phosphorylation and suggests that PINK1-Drp1S616 phosphorylation coupling is essential for convergence between mitochondrial dynamics and neural circuitry formation and refinement. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2059-3635 |
| Relation: | https://doaj.org/toc/2059-3635 |
| DOI: | 10.1038/s41392-022-00933-z |
| URL الوصول: | https://doaj.org/article/9b517743004542d08173e9828fe97322 |
| رقم الأكسشن: | edsdoj.9b517743004542d08173e9828fe97322 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20593635 |
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| DOI: | 10.1038/s41392-022-00933-z |