ATF4 Selectively Regulates Heat Nociception and Contributes to Kinesin-mediated TRPM3 Trafficking

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Mar 4

PMID 33658516

Citations 12

Authors

Man-Xiu Xie

Xian-Ying Cao

Wei-An Zeng

Ren-Chun Lai

Lan Guo

Jun-Chao Wang

Yi-Bin Xiao

Xi Zhang

Di Chen

Xian-Guo Liu

Xiao-Long Zhang

Affiliations

Soon will be listed here.

Abstract

Effective treatments for patients suffering from heat hypersensitivity are lacking, mostly due to our limited understanding of the pathogenic mechanisms underlying this disorder. In the nervous system, activating transcription factor 4 (ATF4) is involved in the regulation of synaptic plasticity and memory formation. Here, we show that ATF4 plays an important role in heat nociception. Indeed, loss of ATF4 in mouse dorsal root ganglion (DRG) neurons selectively impairs heat sensitivity. Mechanistically, we show that ATF4 interacts with transient receptor potential cation channel subfamily M member-3 (TRPM3) and mediates the membrane trafficking of TRPM3 in DRG neurons in response to heat. Loss of ATF4 also significantly decreases the current and KIF17-mediated trafficking of TRPM3, suggesting that the KIF17/ATF4/TRPM3 complex is required for the neuronal response to heat stimuli. Our findings unveil the non-transcriptional role of ATF4 in the response to heat stimuli in DRG neurons.

Citing Articles

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