- Solubilized proteins from PC12 membranes.
- 1 µl/1x106 cells (1: 50).
- Cell surface detection of p75NTR in live PC12 cells:___ Unstained cells.
___ Cells + Mouse Anti-Rat p75 NGF Receptor (extracellular)-FITC Antibody (#AN-170-F) 1 µl/1x106 cells (1:50).
p75NTR known as a cell surface receptor for NGF, BDNF, NT-3 and NT-4, is also a receptor for β-amyloid, and for the myelin axon repellant protein MAG.1,2,4,6
Binding of neurotrophins induces receptor dimerization followed by phosphorylation of receptor kinase residues and recruitment of intracellular proteins involved in signal transduction.
p75NTR functions alone, or in functional complexes with the neurotrophin receptors trkA, trkB and trkC. p75NTR signals via interaction with different transducers such as TRAF6, IRAK, and RIP-2, activating NF-κB, JNK and p38, and inactivating rhoA.1,3,6
Receptor degradation is mediated by a metalloproteinase-dependent shedding of the extracellular domain.
p75NTR binds all neurotrophins with similar nM affinity, but binds pro-neurotrophins with greater affinity, and is more potently activated by pro-neurotrophins.5
Overexpression of the intracellular domain in developing neurons induces apoptosis.
NGF-dependent association of NRIF with p75NTR contributes to pro-apoptotic signaling.7,8 β-amyloid peptide binds p75NTR and stimulates pro-apoptotic signaling by p75NTR, suggesting that the receptor may be relevant for Alzheimer's disease.9