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

doi:10.1016/S0896-6273(03)00770-0

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 journal › Article › peer-review

429 Scopus citations

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 language	English
Pages (from-to)	1095-1104
Number of pages	10
Journal	Neuron
Volume	40
Issue number	6
DOIs	https://doi.org/10.1016/S0896-6273(03)00770-0
State	Published - 18 Dec 2003
Externally published	Yes

Funding

Funders	Funder number
NIH/NINDS
Y. Leon Benoziyo Institute for Molecular Medicine, the Irwin Green Alzheimer's Research Fund
National Institute of Neurological Disorders and Stroke	R01NS041596
Minerva Foundation

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10.1016/S0896-6273(03)00770-0

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title = "Axoplasmic importins enable retrograde injury signaling in lesioned nerve",

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.",

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

note = "Funding Information: We thank Moses Chao, Enno Hartmann, and Carlos Ibanez for helpful comments on the early drafts of this manuscript; Karsten Weis, Ziv Reich, Michael Elbaum, Irith Ginzburg, and Elior Peles for generous gifts of reagents, Vladimir Kiss for highly professional guidance on confocal microscopy, and Zehava Levy for excellent technical assistance. M.F. is the incumbent of the Daniel E. Koshland Sr. Career Development Chair at the Weizmann Institute. Supported by grants from the Y. Leon Benoziyo Institute for Molecular Medicine, the Irwin Green Alzheimer's Research Fund, and the Minerva Foundation (to M.F.), and by NIH/NINDS NS41596 (to J.L.T.).",

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AU - Hanz, Shlomit

AU - Perlson, Eran

AU - Willis, Dianna

AU - Zheng, Jun Qi

AU - Massarwa, R'ada

AU - Huerta, Juan J.

AU - Koltzenburg, Martin

AU - Kohler, Matthias

AU - Van-Minnen, Jan

AU - Twiss, Jeffery L.

AU - Fainzilber, Mike

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N2 - 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.

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Axoplasmic importins enable retrograde injury signaling in lesioned nerve

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