Reactome: A Curated Pathway Database

p75 NTR receptor-mediated signalling (R-HSA-193704)

Species Homo sapiens

Summation

Besides signalling through the tyrosine kinase receptors TRK A, B, and C, the mature neurotrophins NGF, BDNF, and NT3/4 signal through their common receptor p75NTR. NGF binding to p75NTR activates a number of downstream signalling events controlling survival, death, proliferation, and axonogenesis, according to the cellular context. p75NTR is devoid of enzymatic activity, and signals by recruiting other proteins to its own intracellular domain. p75 interacting proteins include NRIF, TRAF2, 4, and 6, NRAGE, necdin, SC1, NADE, RhoA, Rac, ARMS, RIP2, FAP and PLAIDD. Here we annotate only the proteins for which a clear involvement in p75NTR signalling was demonstrated.
A peculiarity of p75NTR is the ability to bind the pro-neurotrophins proNGF and proBDNF. Proneurotrophins do not associate with TRK receptors, whereas they efficiently signal cell death by apoptosis through p75NTR. The biological action of neurotrophins is thus regulated by proteolytic cleavage, with proforms preferentially activating p75NTR, mediating apoptosis, and mature forms activating TRK receptors, to promote survival. Moreover, the two receptors are utilised to differentially modulate neuronal plasticity. For instance, proBDNF-p75NTR signalling facilitates LTD, long term depression, in the hippocampus (Woo NH, et al, 2005), while BDNF-TRKB signalling promotes LTP (long term potentiation). Many biological observations indicate a functional interaction between p75NTR and TRKA signaling pathways.

Locations in the PathwayBrowser
Additional Information
GO Biological Process neurotrophin TRK receptor signaling pathway (0048011)
Literature References
pubMedId Title Journal Year
16699811 Neurotrophin signaling: many exciting surprises! Cell Mol Life Sci 2006
12671646 Neurotrophins and their receptors: a convergence point for many signalling pathways Nat Rev Neurosci 2003
16939974 Neurotrophin-regulated signalling pathways Philos Trans R Soc Lond B Biol Sci 2006