Connecting the dots: trafficking of neurotrophins, lectins and diverse pathogens by binding to the neurotrophin receptor p75^NTR

Abstract

The common receptor for neurotrophins, p75, has important roles in internalization and trafficking of neurotrophins along axons. Recent studies show that an astonishing array of proteins, including lectins, pathogens and neurotoxins, bind the p75 receptor, suggesting that they can hijack and utilize this receptor for trafficking between neuronal populations within the nervous system. Such pathogens include the neurologically important rabies viruses, prion proteins, beta-amyloid and possibly tetanus toxin. These proteins may hijack existing transport machineries designed to traffick neurotrophins, thus allowing the infiltration and distribution of pathogens and toxins among vulnerable neuronal populations with devastating effects, as seen in rabies, prion encephalopathies, Alzheimer's disease and tetanic muscle spasm. The discovery of an entry and transport machinery that is potentially shared between pathogens and neurotrophins sheds light ono trafficking systems in the nervous system and may assist the design of novel therapeutic avenues that prevent or slow the progression of diverse chronic and acute neurological disorders.

Cell death in the developing vertebrate retina

“…Thus, anti-NGF or anti-p75 antibodies substantially reduce the number of apoptotic cells in the E6 chick retina 1999). Moreover p75 can bind to other neurotrophins and in that case its effect leads to a neuroprotective action (Butowt and von Bartheld, 2003).…”

Synaptic Targeting of Retrogradely Transported Trophic Factors in Motoneurons: Comparison of Glial Cell Line-Derived Neurotrophic Factor, Brain-Derived Neurotrophic Factor, and Cardiotrophin-1 with Tetanus Toxin

“…This mechanism of transsynaptic transcytosis is particularly prominent in motoneurons (Schwab and Thoenen, 1977a;Schwab et al, 1979). It is likely that neurons developed efficient transcytotic transport pathways for the purpose of trafficking trophic substances across multiple synapses (Schwab and Thoenen, 1977b;Butowt and von Bartheld, 2003;von Bartheld, 2004). However, to date, no trophic factor has been identified with synaptic targeting properties and transcytotic efficiencies that resemble those of tetanus toxin.…”

Rabies Virus Envelope Glycoprotein Targets Lentiviral Vectors to the Axonal Retrograde Pathway in Motor Neurons

“…This pathway is utilized by tetanus neurotoxin (TeNT) and enables this and other pathogens to reach the neuron soma from distal infection sites such as the neuromuscular junction (22)(23)(24)(25)(26)(27)(28). This axonal trafficking pathway, shared by neurotrophins in the CNS (29), utilizes a population of endosomes undergoing a sequential Rab5 and Rab7 transition. In contrast to the canonical pathway, however, this maturation is not accompanied by a decrease in the luminal pH, which remains neutral.…”