Low-affinity nerve growth factor receptor

The Low-Affinity Nerve Growth Factor Receptor (nerve growth factor receptor (TNFR superfamily, member 16), also called the LNGFR or p75 neurotrophin receptor) is one of the two receptor types for the is_associated_with::neurotrophins, a family of protein growth factors that stimulate neuronal cells to survive and differentiate. LNGFR is a member of the tumor necrosis factor receptor (TNF receptor)superfamily - indeed, LNGFR was the first member of this large family of receptors to be characterized.

Neurotrophins
The is_associated_with::neurotrophins are composed of four proteins, all of which bind to the LNGFR: is_associated_with::Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (is_associated_with::BDNF), Neurotrophin-3 (is_associated_with::NT-3), and Neurotrophin-4 (is_associated_with::NT-4).

Nerve growth factor, the prototypical growth factor, is a protein secreted by a neuron's target. NGF is critical for the survival and maintenance of sympathetic and sensory neurons. NGF is released from the target cells, binds to and activates its high-affinity receptor (is_associated_with::TrkA), and is internalized into the responsive neuron. The NGF/is_associated_with::TrkA complex is subsequently trafficked back to the cell body. This movement of NGF from axon tip to soma is thought to be involved in the long-distance signaling of neurons.

The activation of is_associated_with::TrkA by NGF is critical in inducing the survival and differentiation caused by this growth factor.

However, NGF binds at least two receptors on the surface of cells that are capable of responding to this growth factor, is_associated_with::TrkA (pronounced "Track A") and the LNGFR.

Trk family of receptor tyrosine kinases
is_associated_with::TrkA 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 cellular signaling). There are other related Trk receptors, is_associated_with::TrkB and is_associated_with::TrkC. Also, there are other neurotrophic factors structurally related to NGF: is_associated_with::BDNF (for Brain-Derived Neurotrophic Factor), is_associated_with::NT-3 (for Neurotrophin-3) and NT-4 (for Neurotrophin-4). While is_associated_with::TrkA mediates the effects of NGF, is_associated_with::TrkB binds and is activated by is_associated_with::BDNF, NT-4, and is_associated_with::NT-3, and is_associated_with::TrkC binds and is activated only by is_associated_with::NT-3.

Function
Neurotrophins activating LNGFR may signal a cell to die via apoptosis, but this effect is counteracted by anti-apoptotic signaling by is_associated_with::TrkA, is_associated_with::TrkB, or is_associated_with::TrkC signaling in cells that also express those receptors. LNGFR functions in a complex with Nogo receptor (NgR, is_associated_with::Reticulon 4 receptor) to mediate RhoA-dependent inhibition of growth of regenerating axons exposed to inhibitory proteins of CNS myelin, such as Nogo, MAG or OMgP. LNGFR also activates a is_associated_with::caspase- dependent signaling pathway that promotes developmental axon pruning, and axon degeneration in neurodegenerative disease.

Recent research has suggested a number of roles for the LNGFR, including in development of the eyes and sensory neurons, and in repair of muscle and nerve damage in adults.

Two distinct subpopulations of is_associated_with::Olfactory ensheathing glia (being researched for nerve repair) have been identified with high or low cell surface expression of low-affinity nerve growth factor receptor (p75).

Role in cancer stem cells
LNGFR has been implicated as a marker for cancer stem cells in is_associated_with::melanoma and other cancers. Melanoma cells transplanted into an immunodeficient mouse model were shown to require expression of CD271 in order to grow a melanoma. is_associated_with::Gene knockdown of CD271 has also been shown to abolish neural crest stem cell properties of melanoma cells.

Interactions
Low-affinity nerve growth factor receptor has been shown to interact with:


 * is_associated_with::FSCN1,
 * is_associated_with::MAGEH1,
 * NDN,
 * is_associated_with::NGFRAP1
 * NGF,
 * is_associated_with::PRKACB,
 * is_associated_with::TRAF2, and
 * is_associated_with::TRAF4.