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iNature lacks effective treatment for patients with thermal hypersensitivity, which is mainly due to the limited understanding of the pathogenic mechanism of this disease.
In the nervous system, activated transcription factor 4 (ATF4) is involved in the regulation of synaptic plasticity and memory formation.
On March 3, 2021, Liu Xianguo of Sun Yat-sen University and Zhang Xiao-Long of Guangdong Academy of Medical Sciences (Zhang Xiao-Long) jointly published a study titled "ATF4 selectively regulates heat nociception and contributes to kinesin-mediated TRPM3 trafficking" in Nature Communications.
The paper, the research shows that ATF4 plays an important role in thermal nociception.
The loss of ATF4 in mouse dorsal root ganglion (DRG) neurons selectively impairs heat sensitivity.
In terms of mechanism, this study showed that ATF4 interacts with transient receptor potential cation channel subfamily M member 3 (TRPM3) and mediates the membrane transport of TRPM3 by DRG neurons in response to heat.
The loss of ATF4 also significantly reduced current and KIF17-mediated TRPM3 transport, which suggests that the KIF17/ATF4/TRPM3 complex is required for neuronal response to thermal stimuli.
The findings reveal the non-transcriptional role of ATF4 in the response of DRG neurons to thermal stimulation.
Activating transcription factor 4 (ATF4) is a member of the ATF/cAMP response element binding protein (CREB) family.
ATF4 regulates transcription by forming a dimer with its basic leucine zipper (bZIP) domain and its partner.
ATF4 increases the expression of the related transcription factor ATF3.
Together with ATF4, this transcription factor mediates changes in metabolism, cell redox state and apoptosis-related gene expression levels, which is conducive to stress adaptation.
ATF4 plays a role in a variety of tissues.
.
The bone and lens development of ATF4 knockout mice is severely impaired.
In the nervous system, ATF4 plays a key role in synaptic plasticity and memory formation.
However, it is unclear whether and how ATF4 is involved in nociception.
Unique membrane proteins in neurons are sensitive to specific stimuli that mediate nociceptive signal transduction.
TRP channels form a variety of cation channel clusters involved in various physiological processes, including sensory neuron stimulation detection, cross-cell cation transport and so on.
Among these proteins, transient receptor potential cation channel subfamily M member 3 (TRPM3) is a non-selective cation channel that can be activated by heating and membrane depolarization.
TRPM3 is expressed at high levels in nociceptive dorsal root ganglion (DRG) neurons, and has recently shown a pain response to heat.
Several TRP subtypes, including TRPM3, are mainly located in the cytoplasm of primary sensory neurons.
Regulating the classification and transport of TRP in cells may significantly change channel function and neuronal excitability.
At present, the mechanism of TRPM3 membrane transport is unclear.
As we all know, kinesin superfamily proteins (KIF) constitute 15 kinesin families, called kinesin 1 to kinesin 14B.
A large part of these kinesin proteins mediate the microtubule-dependent transport of cargo proteins in various cell types.
.
The motor protein KIF13B has been shown to mediate TRPV1 membrane transport and does not affect the expression of total TRPV1 in DRG neurons.
Previous studies have shown that overexpression of KIF5B improves the cell surface and axon distribution of Nav1.
8, while the inhibitory effect of KIF5B reduces the current density of Nav1.
8 in DRG neurons. These results indicate that the anterograde axon transport of Nav1.
8 occurs through a mechanism involving motor proteins.
Studies have shown that KIF3A-mediated transport of Nav1.
6 in DRG neurons is related to chronic pain.
Kinesin 2 family protein KIF17 is mainly located in the body and dendrites of neurons.
It has been shown that KIF17 plays an important role in the distribution of NR2B, GluR5 and Kv4.
2 in distal dendrites.
In addition, KIF17 interacts with nuclear RNA export factor 2 (NXF2), enabling the bidirectional transport of mRNA in dendrites.
KIF17 also mediates the transport of goods from the inside of the flagella to the distal end of the flagella or cilia, thereby regulating the function of the flagella.
However, the role of KIF motor protein in TRPM3 membrane transport is unclear.
In this study, it was revealed that ATF4 controls thermal sensitivity, but not mechanical sensitivity.
In addition, ATF4 mediates the membrane localization of TRPM3 in DRG neurons by interacting with the motor protein KIF17, thereby contributing to thermal sensitivity.
In the end, this research work revealed the cellular mechanisms necessary for thermal nociception.
Reference message: https://
In the nervous system, activated transcription factor 4 (ATF4) is involved in the regulation of synaptic plasticity and memory formation.
On March 3, 2021, Liu Xianguo of Sun Yat-sen University and Zhang Xiao-Long of Guangdong Academy of Medical Sciences (Zhang Xiao-Long) jointly published a study titled "ATF4 selectively regulates heat nociception and contributes to kinesin-mediated TRPM3 trafficking" in Nature Communications.
The paper, the research shows that ATF4 plays an important role in thermal nociception.
The loss of ATF4 in mouse dorsal root ganglion (DRG) neurons selectively impairs heat sensitivity.
In terms of mechanism, this study showed that ATF4 interacts with transient receptor potential cation channel subfamily M member 3 (TRPM3) and mediates the membrane transport of TRPM3 by DRG neurons in response to heat.
The loss of ATF4 also significantly reduced current and KIF17-mediated TRPM3 transport, which suggests that the KIF17/ATF4/TRPM3 complex is required for neuronal response to thermal stimuli.
The findings reveal the non-transcriptional role of ATF4 in the response of DRG neurons to thermal stimulation.
Activating transcription factor 4 (ATF4) is a member of the ATF/cAMP response element binding protein (CREB) family.
ATF4 regulates transcription by forming a dimer with its basic leucine zipper (bZIP) domain and its partner.
ATF4 increases the expression of the related transcription factor ATF3.
Together with ATF4, this transcription factor mediates changes in metabolism, cell redox state and apoptosis-related gene expression levels, which is conducive to stress adaptation.
ATF4 plays a role in a variety of tissues.
.
The bone and lens development of ATF4 knockout mice is severely impaired.
In the nervous system, ATF4 plays a key role in synaptic plasticity and memory formation.
However, it is unclear whether and how ATF4 is involved in nociception.
Unique membrane proteins in neurons are sensitive to specific stimuli that mediate nociceptive signal transduction.
TRP channels form a variety of cation channel clusters involved in various physiological processes, including sensory neuron stimulation detection, cross-cell cation transport and so on.
Among these proteins, transient receptor potential cation channel subfamily M member 3 (TRPM3) is a non-selective cation channel that can be activated by heating and membrane depolarization.
TRPM3 is expressed at high levels in nociceptive dorsal root ganglion (DRG) neurons, and has recently shown a pain response to heat.
Several TRP subtypes, including TRPM3, are mainly located in the cytoplasm of primary sensory neurons.
Regulating the classification and transport of TRP in cells may significantly change channel function and neuronal excitability.
At present, the mechanism of TRPM3 membrane transport is unclear.
As we all know, kinesin superfamily proteins (KIF) constitute 15 kinesin families, called kinesin 1 to kinesin 14B.
A large part of these kinesin proteins mediate the microtubule-dependent transport of cargo proteins in various cell types.
.
The motor protein KIF13B has been shown to mediate TRPV1 membrane transport and does not affect the expression of total TRPV1 in DRG neurons.
Previous studies have shown that overexpression of KIF5B improves the cell surface and axon distribution of Nav1.
8, while the inhibitory effect of KIF5B reduces the current density of Nav1.
8 in DRG neurons. These results indicate that the anterograde axon transport of Nav1.
8 occurs through a mechanism involving motor proteins.
Studies have shown that KIF3A-mediated transport of Nav1.
6 in DRG neurons is related to chronic pain.
Kinesin 2 family protein KIF17 is mainly located in the body and dendrites of neurons.
It has been shown that KIF17 plays an important role in the distribution of NR2B, GluR5 and Kv4.
2 in distal dendrites.
In addition, KIF17 interacts with nuclear RNA export factor 2 (NXF2), enabling the bidirectional transport of mRNA in dendrites.
KIF17 also mediates the transport of goods from the inside of the flagella to the distal end of the flagella or cilia, thereby regulating the function of the flagella.
However, the role of KIF motor protein in TRPM3 membrane transport is unclear.
In this study, it was revealed that ATF4 controls thermal sensitivity, but not mechanical sensitivity.
In addition, ATF4 mediates the membrane localization of TRPM3 in DRG neurons by interacting with the motor protein KIF17, thereby contributing to thermal sensitivity.
In the end, this research work revealed the cellular mechanisms necessary for thermal nociception.
Reference message: https://
