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 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.
authors.affiliation: Molecular Neurobiology Group, Department of Biological Chemistry, Weizmann Institute of Science, 76100, Rehovot, Israel.
authors.forename: Shlomit
authors.initials: S
authors.lastname: Hanz
authors.forename: Eran
authors.initials: E
authors.lastname: Perlson
authors.forename: Dianna
authors.initials: D
authors.lastname: Willis
authors.forename: Jun-Qi
authors.initials: JQ
authors.lastname: Zheng
authors.forename: R'ada
authors.initials: R
authors.lastname: Massarwa
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Huerta
authors.forename: Martin
authors.initials: M
authors.lastname: Koltzenburg
authors.forename: Matthias
authors.initials: M
authors.lastname: Kohler
authors.forename: Jan
authors.initials: J
authors.lastname: van-Minnen
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Twiss
authors.forename: Mike
authors.initials: M
authors.lastname: Fainzilber
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D028884:Karyopherins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012183:Retrograde Degeneration / Q000235:genetics / Q000378:metabolism*; D020426:Sciatic Neuropathy / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D028884:Karyopherins; D012333:RNA, Messenger