Evidence for phosphatidylinositol 4-kinase and actin involvement in the regulation of 125I-beta-nerve growth factor retrograde axonal transport.
The signaling events regulating the retrograde axonal transport of neurotrophins are poorly understood, but a role for phosphatidylinositol kinases has been proposed. In this study, we used phenylarsine oxide (PAO) to examine the participation of phosphatidylinositol 4-kinases in nerve growth factor (NGF) retrograde axonal transport within sympathetic and sensory neurons. The retrograde transport of 125I-labeled betaNGF was inhibited by PAO (0.5-2 nmol/eye), and this effect was diminished by dilution. Coinjection of 2,3-dimercaptopropanol with PAO reduced its ability to inhibit 125I-betaNGF retrograde transport. PAO (20 nM to 200 microM) also inhibited NGF-dependent survival of both sympathetic and sensory neuronal populations. F-actin staining in sympathetic and sensory neuronal growth cones was disrupted by PAO at 10 and 2 nM, respectively, and occurred within 5 min of exposure to the drug. The actin inhibitor latrunculin A also rapidly affected F-actin staining in vitro and reduced 125I-betaNGF retrograde axonal transport in vivo to the same extent as PAO. These results suggest that both phosphatidylinositol 4-kinase isoforms and the actin cytoskeleton play significant roles in the regulation of 125I-betaNGF retrograde axonal transport in vivo.
Reynolds
A J
AJ
Developmental Neurobiology Group, Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT.
Heydon
K
K
Bartlett
S E
SE
Hendry
I A
IA
D019870:1-Phosphatidylinositol 4-Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D001370:Axonal Transport / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009414:Nerve Growth Factors / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism; D015398:Signal Transduction; D017783:Superior Cervical Ganglion / Q000378:metabolism
D000199:Actins; D001152:Arsenicals; D004791:Enzyme Inhibitors; D007457:Iodine Radioisotopes; D007527:Isoenzymes; D009414:Nerve Growth Factors; C029341:oxophenylarsine; D019870:1-Phosphatidylinositol 4-Kinase