Human Neurotrophin-4 (NT-4) #3887

Neurotrophins are comprised of at least four family members including NGF, BDNF, NT-3 and NT-4 and all are known to influence growth, development, differentiation and survival of neurons (1). Proneurotrophins bind to p75NTR but not to the family of Trk receptor tyrosine kinases (Trk). Following maturation, NT-3 binds and activates TrkA, TrkB and TrkC, with TrkC almost exclusively binding to NT-3. Mature NT-4 binds to and activates TrkB (2). Trk receptors in turn activate three major signaling pathways: (a) Ras/MAPK, which promotes neuronal differentiation and neurite outgrowth, (b) PI3 Kinase/Akt, which promotes survival and growth of neurons, and (c) PLC-γ 1/PKC, which promotes synaptic plasticity (2).
Unlike knockout mice of other neurotrophins, NT-4^-/- mice do not die early, suggesting that NT-4-dependent neurons are not critical for survival. However, the absence of NT-4 does result in sensory neuron loss (3,4). These mice also have deficits in long-term memory and long-lasting long-term potentiation (L-LTP) in the hippocampus but have normal short term-memory (5).