Copine-6 is a TRPM3 escort protein controlling the sensitivity of sensory neurons to noxious heat
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Updated: Sep 18, 2025

A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice
Published on: March 17, 2015
Yiting Gao1, Shengxiang Yan1, Zhongyang Zhang1
1Department of Pharmacology; The Key Laboratory of New Drug Pharmacology and Toxicology; The Key Laboratory of Neural and Vascular Biology, Ministry of Education; The Hebei Collaboration and Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Diseases, Hebei Medical University, Shijiazhuang, Hebei, China.
Abstract:
Copine-6 is a calcium-sensitive phospholipid-binding protein of the evolutionarily conserved Copine family. In the central nervous system, Copine-6 regulates function of some neurotransmitter receptors and structural plasticity of dendritic spines, influencing learning and memory. Copine-6 is expressed in peripheral somatosensory neurons, but its role in somatosensation remains unclear. Here we demonstrate that Copine-6 plays a prominent role in thermosensation. Copine-6 is highly expressed in a subpopulation of dorsal root ganglia (DRG) neurons that also express thermosensitive TRPM3 channels. Genetic deletion or downregulation of Copine-6 in the DRG in vivo selectively impairs sensitivity to noxious heat, without affecting other sensory modalities, and significantly reduced TRPM3 currents in DRG neurons. Copine-6 interacts with TRPM3 via its von Willebrand factor A (vWA) domain, promoting TRPM3 translocation to the plasma membrane. Thus, Copine-6-dependent TRPM3 trafficking determines noxious-heat sensitivity range of the nerve fibers; moreover, Copine-6 is an accessible target for the treatment of heat hypersensitivity in chronic inflammatory and neuropathic pain.
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