Dual Role, Interactions and Signaling Pathways of p75 NTR in the Nervous System

The p75 neurotrophin receptor (p75NTR) is a 75-kDa glycoprotein and the first identified member of the TNF receptor superfamily. p75NTR is initially expressed very early in embryogenesis in cells derived from all three germinal layers but becomes progressively restricted to specific cell populations such as CNS and PNS. The p75NTR expression is induced after pathologic conditions in a wide variety of cell types. p75NTR is a versatile protein, but its function in different cell types has remained enigmatic. One of the reasons for the lack of clarity regarding the function of p75NTR is that it does not signal by traditional pathways; it has no kinase activity nor is it linked to a G-protein-coupled pathway. p75NTR has no intrinsic enzymatic activity so it depends on its interaction with several adaptor proteins to signal the cascade for neuronal survival or death. The various functions of p75 depend on the type of ligand bound to it (neurotrophins or pro- neurotrophins), the cell type in which it is expressed and the presence or absence of Trk receptor and Interaction with other receptors. This mini-review explores the function, gene expression, interactions with co-receptors and signaling pathways of p75NTR in the nervous system.