Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Copine-6 is a TRPM3 escort protein controlling the sensitivity of sensory neurons to noxious heat

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月19日

查看全文
  • Yiting Gao,
  • Shengxiang Yan,
  • Zhongyang Zhang,
  • Jieyao Zhang,
  • Meng Yang,
  • Shihab Shah,
  • Sofia Figoli,
  • Qi Jing,
  • Haixia Gao,
  • Nikita Gamper

摘要

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.