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proNGF, sortilin, and p75NTR: potential mediators of injury-induced apoptosis in the mouse dorsal root ganglion

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

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Bibliographic Details
Published in:Brain research 2007-10, Vol.1183, p.32-42
Main Authors: Arnett, Melinda G., Ryals, Janelle M., Wright, Douglas E.
Format: Article
Language:English
Online Access:Get full text
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Summary:The nerve growth factor precursor (proNGF) may function as a death-inducing ligand that mediates its apoptotic effects via p75 NTR . ProNGF-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 proNGF. Here, we explore the expression of proNGF, 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 proNGF-induced, p75 NTR -sortilin mediated neuronal death as a critical aspect of nerve-injury induced death in the DRG.
ISSN:0006-8993
DOI:10.1016/j.brainres.2007.09.051