title: Retrograde axonal transport of JNK signaling molecules influence injury induced nuclear changes in p-c-Jun and ATF3 in adult rat sensory neurons.
abstract: In the present study, we investigated if the previously observed JNK-mediated activation of c-Jun and induction of ATF3 could be ascribed to axonal transport of JNK signaling components, or if axonal transport of the transcription factors themselves contributes to the nuclear changes in injured sensory neurons. We observed retrograde axonal transport of a number of JNK upstream kinases in ligated rat sciatic nerve. In these preparations, axonal transport of JNK/p-JNK, the JNK scaffolding protein JIP, and the transcription factors ATF3 and ATF2/p-ATF2 was also found. No or little retrograde transport of c-Jun and p-c-Jun was found, whereas an anterograde transport of Hsp27, a protein previously reported in the context of p-c-Jun and ATF3, was observed. In separate experiments, we found that in vitro inhibition of axonal transport or axonal inhibition of JNK reduced the number of p-c-Jun- and ATF3-positive neuronal nuclei. The results suggest that retrograde axonal transport of JNK signaling components contributes to the injury induced c-Jun phosphorylation and ATF3 induction.
authors.affiliation: Department of Cell and Organism Biology, Lund University, Helgonavägen 3B SE-223 62 Lund, Sweden. charlotta.lindwall@cob.lu.se
authors.forename: Charlotta
authors.initials: C
authors.lastname: Lindwall
authors.forename: Martin
authors.initials: M
authors.lastname: Kanje
mesh_terms: D051698:Activating Transcription Factor 2; D051700:Activating Transcription Factor 3; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects / Q000502:physiology*; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008026:Ligation; D009363:Neoplasm Proteins / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D020426:Sciatic Neuropathy / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D051698:Activating Transcription Factor 2; D051700:Activating Transcription Factor 3; D048868:Adaptor Proteins, Signal Transducing; C497107:Atf2 protein, rat; C497108:Atf3 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; C110528:Mapk8ip1 protein, rat; D009363:Neoplasm Proteins; D011500:Protein Synthesis Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D048031:JNK Mitogen-Activated Protein Kinases