title: Sensing nerve injury at the axonal ER: activated Luman/CREB3 serves as a novel axonally synthesized retrograde regeneration signal.
abstract: Luman/cAMP response element binding protein 3 is an endoplasmic reticulum (ER) transmembrane basic leucine zipper transcription factor whose mRNA and protein localize to adult sensory axons, the latter with axonal ER components along the axon length. Here we show that axon-derived Luman plays an important role in relaying information about axonal injury to the neuronal cell body. Axotomy induces axonal Luman synthesis and also release from the axonal ER of Luman's transcriptionally active amino terminus, which is transported to the cell body in an importin-mediated manner. Visualization of the activation and retrograde translocation of Luman into the nucleus in real time both in vivo and in vitro was accomplished using a specially created N- and C-terminal-tagged Luman adenoviral vector. Small interfering RNA used to reduce Luman expression either neuronally or just axonally significantly impaired the ability of 24-h injury-conditioned sensory neurons to extend the regeneration-associated elongating form of axon growth but had no impact on axon outgrowth in naïve neurons. Collectively, these findings link injury-associated axonal ER responses proximal to the site of injury to the intrinsic regenerative growth capacity of adult sensory neurons.
authors.affiliation: Departments of Anatomy and Cell Biology and Cameco Multiple Sclerosis Neuroscience Research Center, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5 Veterinary Microbiology and.
authors.forename: Zhengxin
authors.initials: Z
authors.lastname: Ying
authors.affiliation: Veterinary Microbiology and.
authors.forename: Vikram
authors.initials: V
authors.lastname: Misra
authors.affiliation: Departments of Anatomy and Cell Biology and Cameco Multiple Sclerosis Neuroscience Research Center, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5 valerie.verge@usask.ca.
authors.forename: Valerie M K
authors.initials: VM
authors.lastname: Verge
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D009416:Nerve Regeneration; D059348:Peripheral Nerve Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017434:Protein Structure, Tertiary; D051381:Rats; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D014709:Vero Cells
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein
keywords: axotomy; dorsal root ganglion; sensory neuron; transcription factor