Evidence for Phosphatidylinositol 4‐Kinase and Actin Involvement in the Regulation of 125I‐β‐Nerve Growth Factor Retrograde Axonal Transport

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Abstract
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 βNGF 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‐βNGF retrograde transport. PAO (20 nM to 200 μM) 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‐βNGF 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‐βNGF retrograde axonal transport in vivo.