Role of Importin alpha3 and importin beta 1 in the peripheral sensory neurons

Project 1: Overall, our work showed using three independent approaches that importin α3 mice have a lower basal sensitivity for noxious heat, show a delayed response to capsaicin-induced pain and recover faster with less pain from a neuropathic pain injury. The data further identified a novel role for an importin α3/c-FOS pathway in the transduction of pain signals. Finally, our preliminary drug screen suggest that two FDA-approved drugs, Sulmazole and Sulfamethizole could be used as new therapeutic to tackle acute and chronic pain. Project 2: Here, we found that Importin beta 1 3’ UTR knockout embryonic neurons that were treated with NT3 grow longer neurites in DRG explants in two independent culturing regimes. RNA seq revealed a set of genes enriched in the importin beta 1 3’ UTR knockout with on commonality; almost all the candidate genes show a binding sequence for Krüppel-like factor (KLF6) transcription factor. In wild type DRG neurons, KLF6 protein is localized in the soma and in their terminals in “the growth cone” when treated with normal NT3 supplement. However, when NT3 concentration is lowered, KL6 is absent from the soma and from the growth cone. These results suggest a positive and direct link of NT3 to the expression of KLF6 in the growth-cone.