title: Increases in Retrograde Injury Signaling Complex-Related Transcripts in Central Axons following Injury.
abstract: Axons in the peripheral nervous system respond to injury by activating retrograde injury signaling (RIS) pathways, which promote local axonal protein synthesis (LPS) and neuronal regeneration. RIS is also initiated following injury of neurons in the central nervous system (CNS). However, regulation of the localization of axonal mRNA required for LPS is not well understood. We used a hippocampal explant system to probe the regulation of axonal levels of RIS-associated transcripts following axonal injury. Axonal levels of importinβ1 and RanBP1 were elevated biphasically at 1 and 24 hrs after axotomy. Transcript levels forβ-actin, a prototypic axonally synthesized protein, were similarly elevated. Our data suggest differential regulation of axonal transcripts. At 1 hr after injury, deployment of actinomycin revealed that RanBP1, but not importinβ1, requires de novo mRNA synthesis. At 24 hrs after injury, use of importazole revealed that the second wave of increased axonal mRNA levels required importinβ-mediated nuclear import. We also observed increased importinβ1 axonal protein levels at 1 and 6 hrs after injury. RanBP1 levels and vimentin levels fluctuated but were unchanged at 3 and 6 hrs after injury. This study revealed temporally complex regulation of axonal transcript levels, and it has implications for understanding neuronal response to injury in the CNS.
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.
authors.forename: Gunja K
authors.initials: GK
authors.lastname: Pathak
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Ornstein
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.
authors.forename: Helim
authors.initials: H
authors.lastname: Aranda-Espinoza
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, MD, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Karlsson
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA; Departments of Orthopaedic Surgery and Bioengineering, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Sameer B
authors.identifier: 0000-0001-6613-3904
authors.initials: SB
authors.lastname: Shah
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism*; D019771:Axotomy / Q000379:methods; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D009416:Nerve Regeneration / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000199:Actins