Helmholtz Gemeinschaft


Axoplasmic importins enable retrograde injury signaling in lesioned nerve

Item Type:Article
Title:Axoplasmic importins enable retrograde injury signaling in lesioned nerve
Creators Name:Hanz, S. and Perlson, E. and Willis, D. and Zheng, J.Q. and Massarwa, R. and Huerta, J.J. and Koltzenburg, M. and Koehler, M. and van Minnen, J. and Twiss, J.L. and Fainzilber, M.
Abstract:Axoplasmic proteins containing nuclear localization signals (NLS) signal retrogradely by an unknown mechanism in injured nerve. Here we demonstrate that the importin/karyopherin alpha and beta families underlie this process. We show that importins are found in axons at significant distances from the cell body and that importin beta 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 beta may enable retrograde transport of signals that modulate the regeneration of injured neurons.
Keywords:Axonal Transport, Cultured Cells, Karyopherins, RNA, Messenger, Retrograde Degeneration, Sciatic Neuropathy, Up-Regulation/, Mice, Animals, Rats
Publisher:Cell Press
Page Range:1095-1104
Date:18 December 2003
Official Publication:https://doi.org/10.1016/S0896-6273(03)00770-0
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library