Proteolytic processing of the p75 neurotrophin receptor: A prerequisite for signalling?: Neuronal life, growth and death signalling are crucially regulated by intra-membrane proteolysis and trafficking of p75NTR

The common neurotrophin receptor (p75^NTR) regulates various functions in the developing and adult nervous system. Cell survival, cell death, axonal and growth cone retraction, and regulation of the cell cycle can be regulated by p75^NTR-mediated signals following activation by either mature or pro-neurotrophins and in combination with various co-receptors, including Trk receptors and sortilin. Here, we review the known functions of p75^NTR by cell type, receptor-ligand combination, and whether regulated intra-membrane proteolysis of p75^NTR is required for signalling. We highlight that the generation of the intracellular domain fragment of p75^NTR is associated with many of the receptor functions, regardless of its ligand and co-receptor interactions.