Pro-NGF, sortilin, and p75NTR: 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 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.
Arnett
Melinda G
MG
Department of Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.
Ryals
Janelle M
JM
Wright
Douglas E
DE
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002470:Cell Survival / Q000502:physiology; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020426:Sciatic Neuropathy / Q000473:pathology; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D008562:Membrane Glycoproteins; D020932:Nerve Growth Factor; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D017475:Receptors, Nerve Growth Factor; D000099183:Sortilin; C517634:Ngfr protein, mouse; C489226:pro-nerve growth factor, mouse