Expression of nerve growth factor receptors by Schwann cells of axotomized peripheral nerves: ultrastructural location, suppression by axonal contact, and binding properties

Abstract

Axotomy of sciatic nerve fibers in adult rats induces expression of NGF receptor in the entire population of Schwann cells located distal to the injury (Taniuchi et al., 1986b). In the present study we have used immunocytochemistry, with a monoclonal antibody directed against the rat NGF receptor, to examine axotomized peripheral nerves by light and electron microscopy. We have found that (1) the NGF receptor molecules were localized to the cell surface of Schwann cells forming bands of Bungner; (2) axonal regeneration into the distal portion of sciatic nerve coincided temporally and spatially with a decrease in Schwann cell expression of NGF receptor; (3) Schwann cell NGF receptor could be induced by axotomy of NGF-independent neurons, such as motoneurons and parasympathetic neurons; and (4) the presence of axon-Schwann cell contact was inversely related to expression of Schwann cell NGF receptor. Using biochemical assays we have found that, in striking contrast to peripheral nerves, there was no detectable induction of NGF receptor in the spinal cord and brain after axotomy of NGF receptor-bearing fibers. Filtration assays of 125I-NGF binding to the induced NGF receptors of Schwann cells measured a Kd of 1.5 nM and a fast dissociation rate, both characteristics of class II receptor sites. We conclude that Wallerian degeneration induces Schwann cells, but not central neuroglia, to produce and position upon their plasmalemmal surface the class II NGF receptor molecules. The induction is ubiquitous among Schwann cells, irrespective of the type of axon they originally ensheathed. Expression of Schwann cell NGF receptor is negatively regulated by axonal contact, being induced when axons degenerate and suppressed when regenerating axons grow out along the Schwann cell surface. We propose that the induced NGF receptors function to bind NGF molecules upon the Schwann cell surface and thereby provide a substratum laden with trophic support and chemotactic guidance for regenerating sensory and sympathetic neurons.

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).…”

Negative regulation of myelination: Relevance for development, injury, and demyelinating disease

“…This indicates that in injured nerves Krox-24 or Egr-3 alone can activate p75NTR expression in the absence of the other (Gao et al, 2007;Nikam et al, 1995). p75NTR, which is known to be expressed by immature Schwann cells, is suppressed in myelinating Schwann cells but reactivated in injured nerves Taniuchi et al, 1988). It is therefore possible that Krox-24 and Egr-3 together take part in promoting dedifferentiation.…”

Dual role for p75NTR signaling in survival and cell death: Can intracellular mediators provide an explanation?

“…In many cell types, the upregulation of p75 NTR is observed under pathological or inflammatory conditions (reviewed in Coulson et al, 1999). p75 NTR expression levels have been shown to be elevated in schwann cells after nerve lesions or removal of axonal contact (Lemke and Chao, 1988;Taniuchi et al, 1988) and in oligodendrocytes, microglia, and macrophages in multiple sclerosis (reviewed in Lee et al, 2001). Overall, the ability of p75 NTR to act in a positive or negative manner on cell viability might be influenced by the levels of the two receptors and the availability of specific neurotrophins during different stages of neuronal development (reviewed in: Barrett and Bartlett, 1994;Kaplan and Miller, 1997;Yoon et al, 1998).…”