title: Integration of retrograde axonal and nuclear transport mechanisms in neurons: implications for therapeutics.
abstract: The elongated morphology of neuronal processes imposes a significant challenge for effective intracellular communication between the neurites and the cell body. This problem is especially acute upon injury, when the cell body must receive accurate and timely information on the site and extent of axonal damage to mount an appropriate response. Recent work has demonstrated that nuclear import factors from the importin (karyopherin) alpha and beta families provide a mechanism for retrograde injury signaling. Importins are found throughout axons and dendrites at significant distances from the cell body, and importin beta protein is increased after nerve lesion by local translation of axonal mRNA. This leads to formation of a high-affinity nuclear localization signal (NLS) binding complex that traffics retrogradely due to an interaction of importin alpha with the motor protein dynein. Disruption of the complex with excess NLS peptides delays regeneration of injured sensory neurons. The dual role of importins in retrograde transport in axons and nuclear import in cell bodies suggests new avenues for manipulating intrinsic regeneration mechanisms in the nervous system and may provide a novel route for drug delivery to the CNS.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Shlomit
authors.initials: S
authors.lastname: Hanz
authors.forename: Mike
authors.initials: M
authors.lastname: Fainzilber
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000008:administration & dosage / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D012183:Retrograde Degeneration / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D028884:Karyopherins