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

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Autophagy, Cells, Cultured, Dopaminergic Neurons, HEK293 Cells, Humans, Inflammation, MPTP Poisoning, Male, Mice, Mice, Knockout, Microglia, Microtubule-Associated Proteins, Phosphorylation, Poly I-C, Proto-Oncogene Proteins c-abl, RNA Interference, Reactive Oxygen Species, Signal Transduction, Tumor Necrosis Factor-alpha
Cell Death Differ
Date: Dec. 01, 2016
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