Oral Presentation 2014 International Biophysics Congress

Regulation of forward trafficking and membrane insertion for P2X3 receptor (#104)

Lan Bao 1 , Xu-Qiao Chen 1 , Jingxiang Zhu 1 , Yan Wang 1 , Xu Zhang 2
  1. Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
  2. Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China

Purinergic receptor P2X3 receptor is a ATP-gated nonselective cation channel, abundantly expressed in primary sensory neurons and involved in pain states derived from inflammation and nerve injury. The assembly and trafficking of the P2X3 receptor are important for its function in primary sensory neurons. As an important inflammation mediator, ATP is released from different cell types around primary sensory neurons especially under pathological pain conditions. However, ATP-mediated forward trafficking of the P2X3 receptor and its related molecular mechanisms have not been fully clarified. Here, we have provided evidence for the presence of ATP-induced long-term membrane insertion of the P2X3 receptor via the collaboration of CaMKII╬▒ and caveolin-1. CaMKII╬▒ phosphorylated Thr388 in the C terminus of the rat P2X3 receptor in a tertiary structure-dependent manner and therefore facilitated receptor interaction with the lipid-raft resident protein caveolin-1. Caveolin-1 association was indispensable for both basal and ATP-induced membrane insertion of the P2X3 receptor. Moreover, Thr388 phosphorylation-increased membrane delivery of the P2X3 receptor also promoted coinsertion of the assembled P2X2 receptor and facilitated receptor function. Our study suggests that forward trafficking of the P2X3 receptor is dynamically modulated by ligand, which is potentially interrelated to the sensitization of sensory neurons under pathological conditions.