Low Affinity Nerve Growth Factor Receptor

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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 which 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).

The Neurotrophins

The neurotrophins are comprised of four proteins, all of which bind to the LNGFR: Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3), and Neurotrophin-4 (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 (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 which are capable of responding to this growth factor, TrkA (pronounced "Track A") and the LNGFR.

The Trk family of receptor tyrosine kinases

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.

The role of the LNGFR

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 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 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. [1]

References

[2] Properties of the nerve growth factor receptor. Relationship between receptor structure and affinity. J Biol Chem. 1985 Feb 10;260(3):1917-26.

[3] Gene transfer and molecular cloning of the rat nerve growth factor receptor. 1987 Nature 325, 593 - 597

[4] TrkB mediates BDNF/NT-3-dependent survival and proliferation in fibroblasts lacking the low affinity NGF receptor. Cell. 1991 Jul 26;66(2):405-13.