NRAGE and the cycling side of the neurotrophin receptor p75

Abstract

Following the discovery of nerve growth factor (NGF) in 19601, it was not long before its capacity to support the development of selective neuronal populations was demonstrated. Rapidly, NGF became considered as the founder member of a family of growth factors as other neuro-trophins, BDNF, NT3 and subsequently NT4/5, were identified. However, it was not until the 1980s that the first receptor for NGF was described2. This receptor was initially thought to be specific for NGF but as other members of the neurotrophin family were described it became clear that it could bind all neurotrophins and as such it became known as the neurotrophic receptor p75 (p75NTR). The transcendence of the identification of p75NTR was somehow devalued by the lack of any obvious catalytic motif within its cytoplasmic domain. Indeed, when the Trk family of receptor tyrosine kinases was shown to specifically bind and transduce the trophic signals initiated by the neurotrophins3, p75NTR became a secondary player in studies of the neurotrophin family.