Abstract
The nerve growth factor precursor (pro-NGF) may function as a death-inducing ligand that mediates its apoptotic effects via p75NTR. Pro-NGF-induced apoptosis is postulated to be dependent upon membrane expression of the sortilin receptor, which interacts with p75NTR to promote a high-affinity binding site for pro-NGF. Here, we explore the expression of pro-NGF, sortilin and p75NTR in the mouse lumbar dorsal root ganglion (DRG) to understand the potential for this trimeric signaling complex to function in injury-induced neuronal death of DRG neurons. Our results reveal the expression of all 3 components within the DRG and that a subpopulation of neurons coexpresses sortilin and p75NTR. Following sciatic nerve transection, the expression of these proteins appears insensitive to injury; however, the majority of small p75NTR-sortilin coexpressing neurons are lost 25 days after sciatic nerve transection. These results propose pro-NGF-induced, p75NTR-sortilin-mediated neuronal death as a critical aspect of nerve injury-induced death in the DRG.
MeSH terms
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Adaptor Proteins, Vesicular Transport
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Animals
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Apoptosis / genetics
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Apoptosis / physiology*
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Blotting, Western
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Cell Survival / physiology
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Ganglia, Spinal / metabolism
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Ganglia, Spinal / pathology*
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Immunohistochemistry
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Male
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred C57BL
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Nerve Growth Factor / biosynthesis
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Nerve Growth Factor / genetics
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Nerve Growth Factor / physiology*
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Nerve Tissue Proteins / biosynthesis
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology*
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Protein Precursors / biosynthesis
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Protein Precursors / genetics
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Protein Precursors / physiology*
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Receptors, Nerve Growth Factor / biosynthesis
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Receptors, Nerve Growth Factor / genetics
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Receptors, Nerve Growth Factor / physiology*
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Sciatic Neuropathy / pathology
Substances
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Adaptor Proteins, Vesicular Transport
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Membrane Glycoproteins
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Nerve Tissue Proteins
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Protein Precursors
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Receptors, Nerve Growth Factor
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Ngfr protein, mouse
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pro-nerve growth factor, mouse
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Nerve Growth Factor
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sortilin