p75NTR:: A study in contrasts

The p75 neurotrophin receptor (p75(NTR)) and trkA, trkB and trkC mediate the physiological effects of the neurotrophins. The trk receptors are responsible for the stereotypical survival and growth properties of the neurotrophins but defining the physiological function of the p75(NTR) has,, proven difficult. The p75(NTR) binds each of the neurotrophins with low nanomolar affinity whereas the three trk receptors show strong binding preferences for individual neurotrophins; in some cell types, p75(NTR) is the only neurotrophin receptor whereas in others it is co expressed with the trks. The analysis of p75(NTR) function has been complicated by the fact that the predominant physiological role of p75(NTR) changes dramatically depending on cell context. Available data suggests that in cells where p75(NTR) is co-expressed with trk receptors, p75(NTR) functionally collaborates with the trks to either enhance responses to preferred trk ligands, to reduce neurotrophin-mediated trk receptor activation resulting from non-preferred ligands or to facilitate apoptosis resulting from neurotrophin withdrawal. In cells lacking trk expression, p75(NTR) can act autonomously to activate ligand-dependent signaling cascades that may in some circumstances result in apoptosis but probably not through pathways utilized by its apoptotic brethren in the TNF receptor superfamily. Potential mechanisms for each of these functions of p75(NTR) are considered and the physiological implications of this unique signaling system are discussed.