Related Experiment Video

Updated: Sep 12, 2025

A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice
08:35

A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice

Published on: March 17, 2015

15.0K

Histone lactylation regulates DOCK4 to control heat nociception and supports Dynein-mediated Nav1.7 trafficking

Man-Xiu Xie1, Ren-Chun Lai1, Yi-Bin Xiao2,3

  • 1Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.

Nature Communications
|August 4, 2025
PubMed

Insights

Dedicator of cytokinesis 4 (Dock4) deficiency in sensory neurons enhances heat nociception by altering sodium channel Nav1.7 trafficking. This discovery offers insights into autism-related pain perception.

Area of Science:

  • Neuroscience
  • Pain Research
  • Genetics

Background:

  • Heat nociception relies on thermosensors, but other mechanisms remain unexplored.
  • Autism spectrum disorder (ASD) often involves altered pain perception, with unclear underlying causes.
  • Dedicator of cytokinesis 4 (Dock4) is an autism susceptibility gene implicated in neuronal function.

Purpose of the Study:

  • To investigate the role of Dock4 in heat nociception and its potential link to autism.
  • To elucidate the molecular mechanism by which Dock4 regulates pain perception.

Main Methods:

  • Examined Dock4 levels in dorsal root ganglion (DRG) neurons across pain models.
  • Utilized mouse models with Dock4 deficiency in sensory neurons to assess heat nociception.
  • Investigated the interaction between Dock4, sodium channel Nav1.7, and the motor protein Dynein using biochemical assays.
  • Performed Dock4 knockdown in nonhuman primates to confirm findings in a relevant species.

Main Results:

  • Dock4 levels were decreased in DRG neurons in pain models, linked to histone lactylation.
  • Dock4 deficiency in sensory neurons significantly increased heat nociception in mice.
  • Dock4 acts as an adaptor protein, forming a Dynein/DOCK4/Nav1.7 complex that mediates Nav1.7 trafficking from the membrane to the cytoplasm.
  • Dock4 knockdown in nonhuman primates also enhanced heat nociception.

Conclusions:

  • The Dynein/DOCK4/Nav1.7 complex represents a novel thermosensor-independent pathway regulating heat nociception.
  • Reduced Dock4 expression contributes to heightened heat sensitivity.
  • This mechanism provides crucial insights into the abnormal pain perception observed in autism spectrum disorder.

More Related Videos

An Improved Assay and Tools for Measuring Mechanical Nociception in Drosophila Larvae07:17

An Improved Assay and Tools for Measuring Mechanical Nociception in Drosophila Larvae

Published on: October 29, 2020

4.9K
Local and Global Methods of Assessing Thermal Nociception in Drosophila Larvae10:53

Local and Global Methods of Assessing Thermal Nociception in Drosophila Larvae

Published on: May 18, 2012

16.0K

Related Concept Videos

Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
14.0K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.6K
Nociception01:44

Nociception

Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain.
29.5K
The Nucleosome Core Particle01:12

The Nucleosome Core Particle

Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
1.3K
Pinching-off of Coated Vesicles01:32

Pinching-off of Coated Vesicles

Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
3.2K