pro-NGF, sortilin, and p75 NTR: Potential mediators of injury-induced apoptosis in the mouse dorsal root ganglion

The nerve growth factor precursor (pro-NGF) may function as a death-inducing ligand that mediates its apoptotic effects via p75 NTR. Pro-NGF-induced apoptosis is postulated to be dependent upon membrane expression of the sortilin receptor, which interacts with p75 NTR to promote a high-affinity bind...

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Bibliographic Details
Published inBrain research Vol. 1183; pp. 32 - 42
Main Authors Arnett, Melinda G., Ryals, Janelle M., Wright, Douglas E.
Format Journal Article
LanguageEnglish
Published Elsevier B.V 2007
Subjects
Cell death
DRG
Mouse
p75 NTR
Peripheral nerve
pro-NGF
Sortilin
Peripheral nerve
Mouse
Cell death
p75 NTR
Sortilin
DRG
pro-NGF
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Summary:The nerve growth factor precursor (pro-NGF) may function as a death-inducing ligand that mediates its apoptotic effects via p75 NTR. Pro-NGF-induced apoptosis is postulated to be dependent upon membrane expression of the sortilin receptor, which interacts with p75 NTR to promote a high-affinity binding site for pro-NGF. Here, we explore the expression of pro-NGF, sortilin and p75 NTR 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 p75 NTR. Following sciatic nerve transection, the expression of these proteins appears insensitive to injury; however, the majority of small p75 NTR–sortilin coexpressing neurons are lost 25 days after sciatic nerve transection. These results propose pro-NGF-induced, p75 NTR–sortilin-mediated neuronal death as a critical aspect of nerve injury-induced death in the DRG.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2007.09.051