Retrograde support of neuronal survival without retrograde transport of nerve growth factor.
Application of nerve growth factor (NGF) covalently cross-linked to beads increased the phosphorylation of TrkA and Akt, but not of mitogen-activated protein kinase, in cultured rat sympathetic neurons. NGF beads or iodine-125-labeled NGF beads supplied to distal axons resulted in the survival of over 80% of the neurons for 30 hours, with little or no retrograde transport of iodine-125-labeled NGF; whereas application of free iodine-125-labeled NGF (0.5 nanograms per milliliter) produced 20-fold more retrograde transport, but only 29% of the neurons survived. Thus, in contrast to widely accepted theory, a neuronal survival signal can reach the cell bodies unaccompanied by the NGF that initiated it.
MacInnis
Bronwyn L
BL
Department of Cell Biology, 6-14 Medical Sciences Building, University of Alberta, Edmonton, Alberta, Canada, T6G 2H7.
Campenot
Robert B
RB
D000818:Animals; D001369:Axons / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D003432:Cross-Linking Reagents; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008863:Microspheres; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000378:metabolism; D015398:Signal Transduction; D017783:Superior Cervical Ganglion
D002867:Chromones; D003432:Cross-Linking Reagents; D004791:Enzyme Inhibitors; D007457:Iodine Radioisotopes; D020928:Mitogen-Activated Protein Kinases; D009025:Morpholines; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D020917:Receptor, trkA; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494920:Akt1 protein, rat