ArticleNature communications2025
Histone lactylation regulates DOCK4 to control heat nociception and supports Dynein-mediated Nav1.7 trafficking.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Antigen-Detected NMR for Minimal Epitope Engineering and Structure-Guided Selection of a NaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactate and lactylation in neuropsychiatric disorders: a comprehensive review.Molecular biology reports · 2026Review
- Fecal microbiota transplantation and Akkermansia muciniphila restore neurodevelopment and behavior via the gut-brain axis in autism-like zebrafish.The ISME journal · 2026Article
- Immune-dominated cellular heterogeneity and stromal plasticity in keloid infiltrating and hypercellular zones revealed by single-cell RNA sequencing.Frontiers in immunology · 2026Article
- Beyond inflammation: a comprehensive microglial regulation model in chronic pain.Molecular biology reports · 2025Review
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Authors and funding
13 authors.
Funding
Abstract
Heat nociception involves thermosensors like transient receptor potential channel V1 in dorsal root ganglion (DRG) neurons, but their loss only partially impairs heat sensing, suggesting other mechanisms. Autism frequently involves abnormal pain perception, but its mechanisms remain unclear. Here we show that dedicator of cytokinesis 4 (Dock4), an autism susceptibility gene, is decreased in DRG neurons across multiple pain models via histone H4K8 lactylation. DOCK4 deficiency in sensory neurons increases heat nociception in mice. Mechanistically, DOCK4 interacts with sodium channel Nav1.7 and mediates its trafficking from the membrane to the cytoplasm in DRG neurons. Acting an adaptor protein, DOCK4 binds the motor protein Dynein to form a Dynein/DOCK4/Nav1.7 complex, where Dynein provides the mechanical force for Nav1.7 trafficking. DOCK4 knockdown in sensory neurons also enhances heat nociception in male nonhuman primates. Thus, the Dynein/DOCK4/Nav1.7 complex represents a thermosensor-independent mechanism regulating heat nociception and provides insights into abnormal pain in autism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.