ATF4 selectively regulates heat nociception and contributes to kinesin-mediated TRPM3 trafficking

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Nature communications - 12(2021), 1 vom: 03. März, Seite 1401

Sprache:

Englisch

Beteiligte Personen:

Xie, Man-Xiu [VerfasserIn]
Cao, Xian-Ying [VerfasserIn]
Zeng, Wei-An [VerfasserIn]
Lai, Ren-Chun [VerfasserIn]
Guo, Lan [VerfasserIn]
Wang, Jun-Chao [VerfasserIn]
Xiao, Yi-Bin [VerfasserIn]
Zhang, Xi [VerfasserIn]
Chen, Di [VerfasserIn]
Liu, Xian-Guo [VerfasserIn]
Zhang, Xiao-Long [VerfasserIn]

Links:

Volltext

Themen:

145891-90-3
Activating Transcription Factor 4
Atf4 protein, mouse
CXCR4 protein, mouse
Chemokine CXCL12
Cxcl12 protein, mouse
EC 3.6.4.4
Journal Article
KIF17 protein, mouse
Kinesins
Receptors, CXCR4
Research Support, Non-U.S. Gov't
TRPM Cation Channels
TRPM3 protein, mouse

Anmerkungen:

Date Completed 18.03.2021

Date Revised 26.02.2024

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41467-021-21731-1

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM32215975X