Kabogo DN, Kar S (2005) Sortilin and p75NTR: localization in adult rat brain and their alterations following pharmacological manipulations. Neuroscience 2005 Abstracts 148.14. Society for Neuroscience, Washington, DC.
Summary: Neurotensin receptor-3 is a single trans-membrane domain 100 kDa protein whose structure is identical to the human gp95/sortilin. This receptor is involved in intracellular trafficking of sphingolipid activator proteins, and may have a role in sorting other soluble lysosomal proteins. Recently, it has been shown that sortilin, under in vitro paradigm, acts as a co-receptor and molecular switch governing the low-affinity neurotrophin receptor p75NTR mediated cell death induced by pro-nerve growth factor. However, very little is currently known about the cellular distribution of sortilin and its possible localization in neurons expressing p75NTR and/or cholinergic markers in the adult rat brain. Using western blotting and immunohistochemistry, we report that immunoreactive sortilin is ubiquitously expressed in the adult rat brain, including the cortex, striatum, basal forebrain, hippocampus, brainstem and cerebellum. In the normal brain immunoreactive sortilin is not found to be present in the basal forebrain cholinergic neurons expressing p75NTR but localized in the cholinergic interneurons of the striatum and motoneurons of the brainstem. Additionally, neither the level nor the expression of sortilin is altered following immunotoxin 192-IgG saporin-induced death of the basal forebrain cholinergic neurons. However, systemic administration of kainic acid, a potent neurotoxin, was found to induce the expression of p75NTR in the subset of sortilin-containing striatal cholinergic neurons which are believed to undergo apoptosis. These results, taken together, suggest that sortilin in normal brain is not expressed in p75NTR containing neurons and may differentially influence p75NTR–mediated cell death in the brain.
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