Demonstration of the retrograde transport of nerve growth factor receptor in the peripheral and central nervous system

Abstract

NGF acts on responsive neurons by binding to specific NGF receptors on axonal termini, after which a critical biochemical signal is retrogradely transported to the cell body. The identity of the signal(s) is unknown; candidates include NGF itself or some other "second messenger." A possible second messenger is the NGF receptor. As a first step in assessing the possible role of NGF receptor in the generation of the NGF-dependent signal, and in understanding the economy of NGF receptor synthesis and utilization, we determined whether the NGF receptor is retrogradely transported. Using immunohistochemical staining with a monoclonal antibody (192-IgG) against rat NGF receptor, we looked for accumulation of NGF receptor molecules distal (retrograde transport), as well as proximal (anterograde transport), to sites of axonal ligation or transection. By 10-12 hr in both the ligated sciatic nerve and the lesioned fimbria-fornix, accumulated NGF receptor was detected proximal and distal to the ligation/lesion site. The transported receptor presumably was located in sympathetic and sensory neurons in the sciatic nerve and in forebrain cholinergic neurons projecting from the medial septum to the hippocampus. In both anatomical sites, accumulation of NGF receptor on the proximal (anterograde) side occurred in streams of fine axonal processes, whereas staining on the distal (retrograde) side occurred in varicose or granular configurations. These results raise the possibility that the NGF receptor has a role in the mechanism of NGF beyond the initial binding event at the plasma membrane of the axonal terminus.

Rescue of lesioned septal cholinergic neurons by nerve growth factor: specificity and requirement for chronic treatment

“…Using immunohistochemical methods these receptors were visualized in Schwann cells (Taniuchi et al, 1986b;Heumann et al, 1987). In contrast, after fimbrial transections, NGF-R were found to appear during the first day after lesioning within neuronal fibers distal to the lesion and probably represent retrogradely transported receptors accumulating within severed cholinergic axons (Johnson et al, 1987). In confirmation of these results, we failed to find NGF-R-positive structures in the hippocampus 2 or more days after fimbrial transections in the present study.…”

“…These receptors mediate internalization and retrograde transport of NGF by cholinergic neurons (Schwab et al, 1979;Seiler and Schwab, 1984). The receptors themselves are transported anterogradely and retrogradely within forebrain cholinergic axons (Taniuchi et al, 1986b;Johnson et al, 1987). NGF synthesized by cholinergic target areas was implied in the sprouting of sympathetic fibers into these areas occurring after lesions of cholinergic pathways (Crutcher, 1987).…”

Post Traumatic Stress Disorder (PTSD) as an Over Activation of Sympathetic Nervous System: An Alternative View

“…NGF is involved in a variety of signaling events such as cell differentiation and survival, growth cessation, and apoptosis of neurons [27] Retrograde transport of NGF has been demonstrated from the intracerebral site to the stellate ganglion [28] Once in the stellate ganglion, NGF is known to promote sprouting (new nerve growth) at the sympathetic end terminals [29]. Sympathetic neurite outgrowth is known to secrete NE as a representative of SNS (Champlain 1972) [30].…”

Circular dichroism and crosslinking studies of the interaction between four neurotrophins and the extracellular domain of the low‐affinity neurotrophin receptor

“…These possibilities include concentration and presentation of neurotrophins (Taniuchi et al, 1988), G-protein-coupled signaling (Feinstein & Larhammer, 1990), retrograde neurotrophin transport (Johnson et al, 1987), discrimination between neurotrophins (Rodriguez-Tebar et al, 1992), association with signaling components or Trk substrates (Ohmichi et al, 1991), association with other kinases (Volonte et al, 1993), cellular specificity (Ip et al, 1993), programmed cell death (Rabizadeh et al, 1993), and neuronal excitation (Palmer et al, 1993). Such receptormediated responses may involve conformational changes induced by ligand binding (Yarden & Ullrich, 1988).…”