Neurotrophin-3

Neurotrophin-3 is a is_associated_with::protein that in humans is encoded by the NTF3 is_associated_with::gene.

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

Function
Although the vast majority of neurons in the is_associated_with::mammalian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural is_associated_with::stem cells; a process known as is_associated_with::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 (is_associated_with::TrkC and is_associated_with::TrkB - see below).

Mice born without the ability to make NT-3 have loss of is_associated_with::proprioceptive and subsets of is_associated_with::mechanoreceptive sensory neurons.

Mechanism of action
NT-3 binds three receptors on the surface of cells which are capable of responding to this growth factor:


 * is_associated_with::TrkC (pronounced "Track C"), is apparently the "physiologic" receptor, in that it binds with greatest affinity to NT-3.


 * However, NT-3 is capable of binding and signaling through a TrkC-related receptors called is_associated_with::TrkB.


 * Finally, NT-3 also binds a second-receptor type besides Trk receptors, called the is_associated_with::LNGFR (for "low affinity nerve growth factor receptor).

High affinity receptors
is_associated_with::TrkC is a is_associated_with::receptor tyrosine kinase (meaning it mediates its actions by causing the addition of phosphate molecules on certain tyrosines in the cell, activating is_associated_with::cellular signaling).

As mentioned above, there are other related Trk receptors, is_associated_with::TrkA and is_associated_with::TrkB. Also as mentioned, there are other neurotrophic factors structurally related to NT-3:
 * NGF (for "Nerve Growth Factor")
 * is_associated_with::BDNF (for "Brain Derived Neurotrophic Factor")
 * is_associated_with::NT-4 (for "Neurotrophin-4")

While TrkB mediates the effects of BDNF, NT-4, and NT-3,  is_associated_with::TrkA binds and is activated by NGF, and TrkC binds and is activated only by NT-3.

Low affinity receptors
The other NT-3 receptor, the is_associated_with::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 is_associated_with::homodimer around which two is_associated_with::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 is_associated_with::apoptosis - so therefore cells expressing the LNGFR in the absence of Trk receptors may die rather than live in the presence of a neurotrophin.