Axoplasmic importins enable retrograde injury signaling in lesioned nerve

Shlomit Hanz, Eran Perlson, Dianna Willis, Jun Qi Zheng, R'ada Massarwa, Juan J. Huerta, Martin Koltzenburg, Matthias Kohler, Jan Van-Minnen, Jeffery L. Twiss, Mike Fainzilber*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Axoplasmic proteins containing nuclear localization signals (NLS) signal retrogradely by an unknown mechanism in injured nerve. Here we demonstrate that the importin/karyopherin α and β families underlie this process. We show that importins are found in axons at significant distances from the cell body and that importin β protein is increased after nerve lesion by local translation of axonal mRNA. This leads to formation of a high-affinity NLS binding complex that traffics retrogradely with the motor protein dynein. Trituration of synthetic NLS peptide at the injury site of axotomized dorsal root ganglion (DRG) neurons delays their regenerative outgrowth, and NLS introduction to sciatic nerve concomitantly with a crush injury suppresses the conditioning lesion induced transition from arborizing to elongating growth in L4/L5 DRG neurons. These data suggest a model whereby lesion-induced upregulation of axonal importin β may enable retrograde transport of signals that modulate the regeneration of injured neurons.

Original languageEnglish
Pages (from-to)1095-1104
Number of pages10
JournalNeuron
Volume40
Issue number6
DOIs
StatePublished - 18 Dec 2003
Externally publishedYes

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