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PINK1-mediated Drp1S616 phosphorylation modulates synaptic development and plasticity via promoting mitochondrial fission

by Liao, Panlin , Lu, Youming , Ke, Xiao , Tian, Runyi , Huang, Taosheng , Zhang, Zhuohua , Wang, Caifang , Wang, Fang , Zhang, Tongmei , He, Yuhong , Zeng, Fangfang , Slone, Jesse , Li, Zhuo , Li, Jiada , Han, Hailong , Tan, Jieqiong , Hu, Zhonghua , Gao, Qingtao , Li, Xiangyu , Chen, Ye , Zhang, Kexuan , Fu, Shiqing , Yang, Yingxuan

in 631/378/87 / 631/80 / Cancer Research / Cell Biology / Dendritic spines / Developmental plasticity / Internal Medicine / Localization / Long-term potentiation / Medicine / Medicine & Public Health / Mitochondria / Neural networks / Oncology / Pathology / Phosphorylation / PTEN-induced putative kinase / Synaptic plasticity / Synaptic strength / Synaptic vesicles / Synaptogenesis

2022

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2022

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2022

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Journal Article

PINK1-mediated Drp1S616 phosphorylation modulates synaptic development and plasticity via promoting mitochondrial fission

Liao, Panlin,

Lu, Youming,

Ke, Xiao,

Tian, Runyi,

Huang, Taosheng,

Zhang, Zhuohua,

Wang, Caifang,

Wang, Fang,

Zhang, Tongmei,

He, Yuhong,

Zeng, Fangfang,

Slone, Jesse,

Li, Zhuo,

Li, Jiada,

Han, Hailong,

Tan, Jieqiong,

Hu, Zhonghua,

Gao, Qingtao,

Li, Xiangyu,

Chen, Ye,

Zhang, Kexuan,

Fu, Shiqing,

Yang, Yingxuan

2022

Overview

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 Drp1 S616 phosphorylation in a PINK1-dependent manner. Moreover, phosphor-mimetic Drp1 S616D 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-Drp1 S616 phosphorylation coupling is essential for convergence between mitochondrial dynamics and neural circuitry formation and refinement.

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Publisher

Nature Publishing Group UK,Nature Publishing Group

Subject

/ 631/80

/ Developmental plasticity

/ Internal Medicine