Endophilin A2 controls touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking

• DOI: 10.1186/s40779-024-00520-z
• Publication Date: 2024-03-12T06:43:33Z
• Authors: Man-Xiu Xie; Ren-Chun Lai; Yi-Bin Xiao; Xi Zhang; Xian-Ying Cao; Xiao-Yu Tian; An-Nan Chen; Zi-Yi Chen; Yan Cao; Xiao Li; Xiao-Long Zhang
• Keywords: Dorsal root ganglion; Kinesin; Allodynia

Abstract Background Tactile and mechanical pain are crucial to our interaction with the environment, yet underpinning molecular mechanism is still elusive. Endophilin A2 (EndoA2) an evolutionarily conserved protein that documented in endocytosis pathway. However, role of EndoA2 regulation sensitivity its underlying mechanisms currently unclear. Methods Male female C57BL/6 mice (8–12 weeks) male cynomolgus monkeys (7–10 years old) were used experiments. Nerve injury-, inflammatory-, chemotherapy-induced pathological models established for this study. Behavioral tests touch, pain, heat cold performed nonhuman primates. Western blotting, immunostaining, co-immunoprecipitation, proximity ligation patch-clamp recordings gain insight into mechanisms. Results The results showed was primarily distributed neurofilament-200-positive (NF200 + ) medium-to-large diameter dorsal root ganglion (DRG) neurons humans. Loss mouse NF200 DRG selectively impaired tactile allodynia. Furthermore, interacted mechanically sensitive ion channel Piezo2 promoted membrane trafficking neurons. Moreover, as adaptor protein, also bound kinesin family member 5B (KIF5B), which involved EndoA2-mediated process Piezo2. damaged Piezo2-mediated rapidly adapting activated currents, re-expression rescued MA currents. In addition, interference suppressed touch hypersensitivity Conclusions Our data reveal KIF5B/EndoA2/Piezo2 complex essential sustaining transmission signals. regulates allodynia via kinesin-mediated sensory findings identify a potential new target treatment pain.