Autophagy regulates MAVS signaling activation in a phosphorylation-dependent manner in microglia

被引：71

作者：

Cheng, Jinbo ^{[1
]}

Liao, Yajin ^{[1
,2
]}

Xiao, Lei ^{[1
]}

Wu, Rong ^{[1
,2
]}

Zhao, Siqi ^{[1
,3
]}

Chen, Hong ^{[1
]}

Hou, Baidong ^{[4
]}

Zhang, Xia ^{[5
,6
]}

Liang, Chengyu ^{[7
]}

Xu, Yun ^{[8
]}

Yuan, Zengqiang ^{[1
,3
]}

机构：

[1] Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100101, Peoples R China

[2] Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China

[3] Beijing Inst Brain Disorders, Ctr Alzheimers Dis, Beijing 100069, Peoples R China

[4] Chinese Acad Sci, Inst Biophys, Key Lab Infect & Immun, Beijing 100101, Peoples R China

[5] Univ Ottawa, Dept Psychiat, Inst Mental Hlth Res Royal, Ottawa, ON K1Z 7K4, Canada

[6] Univ Ottawa, Dept Cellular & Mol Med, Inst Mental Hlth Res Royal, Ottawa, ON K1Z 7K4, Canada

[7] Univ Southern Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA

[8] Nanjing Med Univ, Dept Neurol, Affiliated Drum Tower Hosp, Nanjing 210008, Jiangsu, Peoples R China

来源：

CELL DEATH AND DIFFERENTIATION | 2017年 / 24卷 / 02期

关键词：

CENTRAL-NERVOUS-SYSTEM; NEURONAL CELL-DEATH; PARKINSONS-DISEASE; C-ABL; DOPAMINERGIC DEGENERATION; NEURODEGENERATIVE DISEASE; NLRP3; INFLAMMASOME; OXIDATIVE STRESS; I INTERFERON; PROTEIN;

D O I：

10.1038/cdd.2016.121

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Mitochondrial antiviral signaling (MAVS) protein has an important role in antiviral immunity and autoimmunity. However, the pathophysiological role of this signaling pathway, especially in the brain, remains elusive. Here we demonstrated that MAVS signaling existed and mediated poly(I: C)-induced inflammation in the brain. Along with the MAVS signaling activation, there was an induction of autophagic activation. Autophagy negatively regulated the activity of MAVS through direct binding of LC3 to the LIR motif Y(9) xxI(12) of MAVS. We also found that c-Abl kinase phosphorylated MAVS and regulated its interaction with LC3. Interestingly, tyrosine phosphorylation of MAVS was required for downstream signaling activation. Importantly, in vivo data showed that the deficiency of MAVS or c-Abl prevented MPTP-induced microglial activation and dopaminergic neuron loss. Together, our findings reveal the molecular mechanisms underlying the regulation of MAVS-dependent microglial activation in the nervous system, thus providing a potential target for the treatment of microglia-driven inflammatory brain diseases.

引用

页码：276 / 287

页数：12

共 58 条

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