Recent advances in understanding neurotrophin signaling

The nerve growth factor family of growth factors, collectively known as neurotrophins, are evolutionarily ancient regulators with an enormous range of biological functions. Reflecting this long history and functional diversity, mechanisms for cellular responses to neurotrophins are exceptionally complex. Neurotrophins signal through p75 (NTR), a member of the TNF receptor superfamily member, and through receptor tyrosine kinases (TrkA, TrkB, TrkC), often with opposite functional outcomes. The two classes of receptors are activated preferentially by proneurotrophins and mature processed neurotrophins, respectively. However, both receptor classes also possess neurotrophin-independent signaling functions. Signaling functions of p75 (NTR) and Trk receptors are each influenced by the other class of receptors. This review focuses on the mechanisms responsible for the functional interplay between the two neurotrophin receptor signaling systems.