Signalling through the neurotrophin receptor p75(NTR)

Activation of specific tyrosine kinase receptors by neurotrophins accounts for the longest known biological actions of the neurotrophins, in particular the promotion of neuronal survival. However, recent studies have revealed that nerve growth factor, the neurotrophin regarded as best understood, also activates a signalling pathway by binding to the neurotrophin receptor p75(NTR). This receptor belongs to the tumor necrosis factor receptor family and lacks intrinsic catalytic activity. The p75(NTR) receptor binds all neurotrophins with nanomolar affinity; however, nerve growth factor seems to be uniquely able to activate it, causing the death of trkA-negative neurons during normal development. Thus, nerve growth factor prevents programmed cell death through its receptor TrkA, but promotes it by signalling through p75(NTR).