Article thumbnail
Location of Repository

Can Molecular Motors Drive Distance Measurements in Injured Neurons?

By Naaman Kam, Yitzhak Pilpel and Mike Fainzilber

Abstract

Injury to nerve axons induces diverse responses in neuronal cell bodies, some of which are influenced by the distance from the site of injury. This suggests that neurons have the capacity to estimate the distance of the injury site from their cell body. Recent work has shown that the molecular motor dynein transports importin-mediated retrograde signaling complexes from axonal lesion sites to cell bodies, raising the question whether dynein-based mechanisms enable axonal distance estimations in injured neurons? We used computer simulations to examine mechanisms that may provide nerve cells with dynein-dependent distance assessment capabilities. A multiple-signals model was postulated based on the time delay between the arrival of two or more signals produced at the site of injury–a rapid signal carried by action potentials or similar mechanisms and slower signals carried by dynein. The time delay between the arrivals of these two types of signals should reflect the distance traversed, and simulations of this model show that it can indeed provide a basis for distance measurements in the context of nerve injuries. The analyses indicate that the suggested mechanism can allow nerve cells to discriminate between distances differing by 10% or more of their total axon length, and suggest that dynein-based retrograde signaling in neurons can be utilized for this purpose over different scales of nerves and organisms. Moreover, such a mechanism might also function in synapse to nucleus signaling in uninjured neurons. This could potentially allow a neuron to dynamically sense the relative lengths of its processes on an ongoing basis, enabling appropriate metabolic output from cell body to processes

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:2718615
Provided by: PubMed Central

Suggested articles

Citations

  1. (2008). A neuron-specific cytoplasmic dynein isoform preferentially transports TrkB signaling endosomes.
  2. (2009). A quantitative examination of the role of cargoexerted forces in axonal transport.
  3. (1977). A quantitative study of retrograde neuronal changes in Clarke’s column.
  4. (1965). A Simplex Method for Function Minimization.
  5. (2008). Action potentials: to the nucleus and beyond.
  6. (2000). Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: A novel neuronal marker of nerve injury.
  7. (2004). Acute physiological response of mammalian central neurons to axotomy: ionic regulation and electrical activity.
  8. (2000). Axonal Regeneration of Retinal Ganglion Cells Depending on the Distance of Axotomy in Adult Hamsters.
  9. (2003). Axoplasmic importins enable retrograde injury signaling in lesioned nerve.
  10. (2008). Caldendrin-Jacob: a protein liaison that couples NMDA receptor signalling to the nucleus.
  11. (1996). CD28/B7 system of T cell costimulation.
  12. (1999). Cell cycle-dependent sequencing of cell fate decisions in Caenorhabditis elegans vulva precursor cells.
  13. (1998). Convergence Properties of the Nelder-Mead Simplex Method in Low Dimensions.
  14. (2003). Corticospinal neurons upregulate a range of growth-associated genes following intracortical, but not spinal, axotomy.
  15. (2004). Cytoplasmic dynein functions as a gear in response to load.
  16. (2000). Dynein-mediated cargo transport in vivo. A switch controls travel distance.
  17. (1991). Expression of the growth-associated protein GAP-43 in adult rat retinal ganglion cells following axon injury.
  18. (2003). Extrinsic regulation of injury/growth-related gene expression in the inferior olive of the adult rat.
  19. (2003). Four-dimensional organization of protein kinase signaling cascades: the roles of diffusion, endocytosis and molecular motors.
  20. (2004). From snails to sciatic nerve: Retrograde injury signaling from axon to soma in lesioned neurons.
  21. (2008). Growth factors and combinatorial therapies for CNS regeneration.
  22. (1999). Influence of the axotomy to cell body distance in rat rubrospinal and spinal motoneurons: differential regulation of GAP-43, tubulins, and neurofilament-M.
  23. (2004). Konnerth A
  24. (2008). Localized regulation of axonal RanGTPase controls retrograde injury signaling in peripheral nerve.
  25. (2006). Long-range signaling by phosphoprotein waves arising from bistability in protein kinase cascades.
  26. (2007). Message in a bottle: long-range retrograde signaling in the nervous system.
  27. (2005). Modeling the signaling endosome hypothesis: why a drive to the nucleus is better than a (random) walk.
  28. (2008). Nerve injury signaling.
  29. (1968). Observations on the nucleolar and total cell body nucleic acid of injured nerve cells.
  30. (2006). Processive bidirectional motion of dynein-dynactin complexes in vitro.
  31. (2007). Regulation of intrinsic neuronal properties for axon growth and regeneration.
  32. (1998). Retrograde regulation of growth-associated gene expression in adult rat Purkinje cells by myelin-associated neurite growth inhibitory proteins.
  33. (2006). Retrograde signaling in injured nerve - the axon reaction revisited.
  34. (2008). Rewiring the injured CNS: lessons from the optic nerve.
  35. (2009). Signaling cascades as cellular devices for spatial computations.
  36. (2004). Signaling endosome hypothesis: A cellular mechanism for long distance communication.
  37. (2006). sorting along the axonal retrograde transport pathway.
  38. (1987). Survival and subsequent regeneration of olfactory neurons after a distal axonal lesion.
  39. (2004). Synapse to nucleus signaling during long-term synaptic plasticity; a role for the classical active nuclear import pathway.
  40. (1984). The axon reaction of the goldfish mauthner cell and factors that influence its morphological variability.
  41. (1971). The axon reaction: a review of the principal features of perikaryal responses to axon injury.
  42. (1997). Timing of c-jun protein induction in lumbar dorsal root ganglia after sciatic nerve transection varies with lesion distance.
  43. (2005). Vimentin-dependent spatial translocation of an activated MAP kinase in injured nerve.
  44. (1970). What is the signal for chromatolysis?

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.