Neurotrophin-3

Protein coding gene in the species Homo sapiens

Neurotrophin 3 is a protein that in humans is encoded by the NTF3 gene. The protein encoded by this gene, NT 3, is a neurotrophic factor in the NGF (Nerve Growth Factor) family of neurotrophins. It is a protein growth factor which has activity on certain neurons of the peripheral and central nervous system; it helps to support the survival and differentiation of existing neurons, and encourages the growth and differentiation of new neurons and synapses. NT 3 was the third neurotrophic factor to be characterized, after nerve growth factor (NGF) and BDNF (Brain Derived Neurotrophic Factor).

Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cells; a process known as neurogenesis. Neurotrophins are chemicals that help to stimulate and control neurogenesis. NT 3 is unique in the number of neurons it can potentially stimulate, given its ability to activate two of the receptor tyrosine kinase neurotrophin receptors (TrkC and TrkB). Mice born without the ability to make NT 3 have loss of proprioceptive and subsets of mechanoreceptive sensory neurons.

The other NT 3 receptor, the LNGFR, plays a somewhat less clear role. Some researchers have shown the LNGFR binds and serves as a "sink" for neurotrophins. The crystal structure of NT 3 shows that NT 3 forms a central homodimer around which two glycosylated p75 LNGFR molecules bind symmetrically. The symmetrical binding takes place along the NT 3 interfaces, resulting in a 2:2 ligand receptor cluster in the center. Cells which express both the LNGFR and the Trk receptors might therefore have a greater activity – since they have a higher "microconcentration" of the neurotrophin. It has also been shown, however, that the LNGFR may signal a cell to die via apoptosis – so therefore cells expressing the LNGFR in the absence of Trk receptors may die rather than live in the presence of a neurotrophin.