The Low-Affinity Nerve Growth Factor Receptor (also called the LNGFR or p75 neurotrophin receptor) is one of the two receptor types for the neurotrophins, a family of protein growth factors that stimulate neuronal cells to survive and differentiate. The precise function of the LNGFR is somewhat controversial, in contrast to the function of the high-affinity receptor family for the neurotrophins, the Trk receptor tyrosine kinases such as TrkA.
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 (TrkA), and is internalized into the responsive neuron. The NGF/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 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, TrkA (pronounced "Track A") and the LNGFR.
TrkA is a 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, TrkB and TrkC. Also, there are other neurotrophic factors structurally related to NGF: BDNF (for Brain-Derived Neurotrophic Factor), NT-3 (for Neurotrophin-3) and NT-4 (for Neurotrophin-4). While TrkA mediates the effects of NGF, TrkB binds and is activated by BDNF, NT-4, and NT-3, and TrkC binds and is activated only by NT-3.
As opposed to TrkA, the LNGFR plays a somewhat less clear role in NGF biology. Some researchers have shown the LNGFR binds and serves as a "sink" for neurotrophins. Cells that 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, in the absence of a co-expressed TrkA, 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.
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.
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