Nerve growth factor receptor
Nerve growth factor receptors are a group of growth factor receptors which specifically bind to neurotrophins.
There are two classes of receptors, p75 and the "Trk" family of Tyrosine kinases receptors.
- p75 is a low affinity neurotrophin receptor, to which all neurotrophins bind. It is a member of the tumour necrosis super family. In some contexts, the phrase "x" only applies to this receptor.[1]
- The Trk family include TrkA, TrkB, and TrkC, and will only bind with specific neurotrophins, but with a much higher affinity. The Trks mediate the functional signals of the neurotrophins.
- NGF binds to TrkA, BDNF and NT-4 bind to TrkB and NT-3 binds to TrkC. In addition NT-3 also binds to and activates TrkA and TrkB but it does so less efficiently.
- Whilst the Trk receptors have a clearly defined trophic role, p75 receptors activate signalling pathways which can also result in apoptosis.
TrkA, B, and C receptors
TrkA is a nuclear receptor (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), and there are other neurotrophic factors structurally related to NGF (BDNF, NT-3, and NT-4)
- TrkA mediates the effects of NGF
- TrkB binds and is activated by BDNF, NT-4, and NT-3
- TrkC binds and is activated only by NT-3
LNGFR receptor
The other NGF receptor, the LNGFR, (for Low affinity nerve growth factor receptor, commonly known as "p75", plays a less clear role.
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.
However, although NGF has been classically described as promoting neuron survival and differentiation, research performed in the early 2000s suggest that NGF with its prodomain attached (proNGF) can elicit apoptosis of cells that are positive for the LNGFR and negative for TrkA.[2]
Secreted proNGF has been demonstrated in a variety of neuronal and non-neuronal cell populations. It has been proposed that secreted proNGF can elicit neuron death in a variety of neurodegenerative conditions, including Alzheimer's disease, following the observation of an increase of proNGF in the nucleus basalis of postmortem Alzheimer's brains.
References
- ↑ Nerve Growth Factor Receptor p75 at the US National Library of Medicine Medical Subject Headings (MeSH)
- ↑ Ibáñez C (2002). "Jekyll-Hyde neurotrophins: the story of proNGF". Trends Neurosci 25 (6): 284–6. doi:10.1016/S0166-2236(02)02169-0. PMID 12086739.
External links
- Nerve Growth Factor Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
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