Molecular mechanism of pain pathway
The primary focus of our research is to study the pain pathways at molecular level. The most recent work includes identification of novel accessory subunits for nociceptive sensory neuron-specific sodium channel NaV1.8 using yeast two-hybrid system. One of these clones is the light chain of annexin II, also known as p11, a membrane trafficking factor. We have discovered a novel regulatory mechanism for voltage-gated sodium channel expression as p11 directly binds to the NaV1.8 and promotes the translocation of the sodium channel to the plasma membrane resulting in functional channel expression. Moreover, the endogenous NaV1.8 current in sensory neurons is inhibited by antisense mRNA down-regulation of p11 expression. Thus, p11-NaV1.8 direct interaction is required for functional expression of NaV1.8 in the plasma membrane of sensory neurons. Drugs that disrupt the NaV1.8-p11 interaction and down-regulate channel expression may be useful as novel pain killers.
We are also working on the composition/structure of neuronal membrane proteins expressed in lipid rafts. The processes that target and anchor sodium channels at nodes of Ranvier are now partly understood, but in contrast the mechanisms that regulate distribution of sodium channels in unmyelinated neurons are largely unknown. The sensory neuron specific sodium channel NaV1.8 is solely expressed in unmyelinated nociceptive neurons. We are using NaV 1.8 as a model system to elucidate the regulatory mechanisms that control selective transport and subcellular localization of channels and receptors in unmyelinated sensory neurons.
- The Wellcome Trust
- The Royal Society
Professor John N Wood, University College London, Molecular Nociception
Professor Iwata, Life Sciences, Imperial College London
Stephen B. McMahon, King's College London, Neuroscience
Edwards, Robert, Chemical Engineering, Imperial College London
ANDREW RICE, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Imperial College London
Research Student Supervision