Abstract
NGF is a target-derived growth factor for developing sympathetic neurons. Here, we show that application of NGF exclusively to distal axons of sympathetic neurons leads to an increase in PI3-K signaling in both distal axons and cell bodies. In addition, there is a more critical dependence on PI3-K for survival of neurons supported by NGF acting exclusively on distal axons as compared to neurons supported by NGF acting directly on cell bodies. Interestingly, PI3-K signaling within both cell bodies and distal axons contributes to survival of neurons. The requirement for PI3-K signaling in distal axons for survival may be explained by the finding that inhibition of PI3-K in the distal axons attenuates retrograde signaling. Therefore, a single TrkA effector, PI3-K, has multiple roles within spatially distinct cellular locales during retrograde NGF signaling.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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Axonal Transport / drug effects
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Axons / drug effects
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Axons / metabolism
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Cell Compartmentation / drug effects
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Cell Survival / drug effects
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Cells, Cultured
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Nerve Growth Factor / metabolism*
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Nerve Growth Factor / pharmacology
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Phosphatidylinositol 3-Kinases / metabolism*
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins*
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Rats
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Receptor, trkA / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Sympathetic Nervous System / cytology
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Sympathetic Nervous System / metabolism*
Substances
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Proto-Oncogene Proteins
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Nerve Growth Factor
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Receptor, trkA
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt