p75NTR

p75 neurotrophin receptor, abbreviated p75NTR and also known as nerve growth factor receptor (NGFR) or CD271, is a cell surface protein of the tumor necrosis factor receptor superfamily. It binds neurotrophins such as NGF, BDNF, NT-3, and NT-4/5, but generally with lower affinity than Trk receptors. The receptor can influence cell survival, apoptosis, neurite outgrowth, and synaptic plasticity, and it often modulates signaling initiated by Trk receptors rather than acting in isolation.

Structurally, p75NTR is a single-pass transmembrane glycoprotein featuring an extracellular cysteine-rich domain that mediates ligand binding and an intracellular region that supports diverse signaling. Its intracellular portion contains motifs related to death domains, enabling activation of multiple downstream pathways depending on context and co-receptors.

Signaling through p75NTR is versatile. It can activate NF-kB, JNK, and p38 MAPK pathways, and it interacts with adaptor proteins such as NRAGE, NRIF, and NADE, as well as with sortilin in certain ligand configurations. When mature neurotrophins bind in the absence of sortilin, signaling can support survival or growth. In the presence of proNGF and sortilin, p75NTR participates in a pro-apoptotic signaling complex that can lead to caspase activation and neuronal pruning. The receptor also modulates cellular responses to neurotrophins by influencing growth cone dynamics.

p75NTR is broadly expressed in the nervous system, including developing neurons, glial cells, and certain neural crest-derived lineages. In cancer, the receptor is used as a marker (CD271) for select stem-like cell populations and can participate in tumor progression and treatment resistance. Its diverse roles make p75NTR a focus of research in neurodevelopment, neurodegeneration, and oncology.