The biological functions and signaling mechanisms of the p75 neurotrophin receptor

Abstract

The p75 neurotrophin receptor (p75NTR) regulates a wide range of cellular functions, including programmed cell death, axonal growth and degeneration, cell proliferation, myelination, and synaptic plasticity. The multiplicity of cellular functions governed by the receptor arises from the variety of ligands and co-receptors which associate with p75NTR and regulate its signaling. P75NTR promotes survival through interactions with Trk receptors, inhibits axonal regeneration via partnerships with Nogo receptor (Nogo-R) and Lingo-1, and promotes apoptosis through association with Sortilin. Signals downstream of these interactions are further modulated through regulated intramembrane proteolysis (RIP) of p75NTR and by interactions with numerous cytosolic partners. In this chapter, we discuss the intricate signaling mechanisms of p75NTR, emphasizing how these signals are differentially regulated to mediate these diverse cellular functions.