Dr. Ashley Kalinski, Ph.D., Research Fellow, presents the Neurology/Neuroscience Research Seminar: "Regulation of dual leucine zipper kinase in axons", Friday, September 21st , 2018

Axons spontaneously regenerate following injury in the peripheral nervous system (PNS), but fail to do so in the central nervous system (CNS). This dichotomy stems from both extrinsic and intrinsic factors, that either aid in or block regeneration. Through manipulation of these factors, axons of the CNS can be coaxed to regenerate. A classical way to do this is through a conditioning injury (CI) of the sciatic nerve. Injury to the sciatic nerve prior to injury of the dorsal column will enhance regeneration of dorsal column axons. The CI stimulates an intrinsic growth response in the dorsal root ganglion (DRG) neurons and this can be seen in in vitro studies of DRG cultures. An important regulator of this response is the dual leucine zipper kinase (DLK).  DLK protein levels rapidly increase in axotomized axons and form a retrograde signaling complex that leads to increased transcription of regeneration-associated genes. However, it is not well understood how DLK is regulated at the axon after injury. Here, we show that DLK mRNA is transported to CI cultured DRG axons and this is through its 5’ untranslated region. DLK’s two 5’UTR variants seem to be differentially regulated in the axons and we have evidence to support that DLK can be translated locally within axons. We suspect that local translation of DLK is a key component of the successful regeneration response in injured peripheral nerves.