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Evidence for Phosphatidylinositol 4‐Kinase and Actin Involvement in the Regulation of 125 I‐β‐Nerve Growth Factor Retrograde Axonal Transport
Author(s) -
Reynolds Anna J.,
Heydon Katharina,
Bartlett Selena E.,
Hendry Ian A.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0730087.x
Subject(s) - phosphatidylinositol , axoplasmic transport , microbiology and biotechnology , actin , nerve growth factor , kinase , neuroscience , growth cone , chemistry , biology , biochemistry , axon , receptor
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 125 I‐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 125 I‐βNGF retrograde transport. PAO (20 n M to 200 μ M ) 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 n M , 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 125 I‐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 125 I‐βNGF retrograde axonal transport in vivo.