neurotrophic factor receptor
{{short description|Group of protein families}}
Neurotrophic factor receptors or neurotrophin receptors are a group of growth factor receptors which specifically bind to neurotrophins (neurotrophic factors).
Two classes of neurotrophic factor receptors are the p75 and the "Trk" families of tyrosine kinase 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.{{MeshName|Nerve+Growth+Factor+Receptor+p75}}
- 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
p75NTR receptor
The Low affinity nerve growth factor receptor commonly known as "p75", can signal for apoptosis or promote neuronal survival. Neurotrophins that interact with p75NTR include NGF, NT-3, BDNF, and NT-4/5.{{cite journal| pmid = 9927421| year = 1999| last1 = Bibel| first1 = M.| last2 = Hoppe| first2 = E.| last3 = Barde| first3 = Y. A.| title = Biochemical and functional interactions between the neurotrophin receptors TRK and p75NTR| journal = The EMBO Journal| volume = 18| issue = 3| pages = 616–22| doi = 10.1093/emboj/18.3.616| pmc = 1171154}} Neurotrophins activating p75NTR may initiate apoptosis (for example, via c-Jun N-terminal kinases signaling), and this effect can be counteracted by anti-apoptotic signaling by TrkA.{{cite journal|pmid=15470142|year=2004|last1=Becker|first1=E. B.|last2=Howell|first2=J.|last3=Kodama|first3=Y.|last4=Barker|first4=P. A.|last5=Bonni|first5=A.|title=Characterization of the c-Jun N-terminal kinase-BimEL signaling pathway in neuronal apoptosis|journal=The Journal of Neuroscience |volume=24|issue=40|pages=8762–70|doi=10.1523/JNEUROSCI.2953-04.2004|pmc=6729963}} Neurotrophin binding to p75NTR can promote neuronal survival (for example, via NF-kB activation).{{cite journal| pmid =10433815| year =1999| last1 =Hamanoue| first1 =M.| last2 =Middleton| first2 =G.| last3 =Wyatt| first3 =S.| last4 =Jaffray| first4 =E.| last5 =Hay| first5 =R. T.| last6 =Davies| first6 =A. M.| title =P75-mediated NF-kappaB activation enhances the survival response of developing sensory neurons to nerve growth factor| journal =Molecular and Cellular Neurosciences| volume =14| issue =1| pages =28–40| doi =10.1006/mcne.1999.0770| s2cid =25648122}}
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.{{cite journal |author=Ibáñez C |title=Jekyll-Hyde neurotrophins: the story of proNGF |journal=Trends Neurosci |volume=25 |issue=6 |pages=284–6 |year=2002 |pmid=12086739 |doi=10.1016/S0166-2236(02)02169-0|s2cid=9449831 }}
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 {{citation needed|date=December 2020}}.
References
{{Reflist|2}}
Further reading
Review papers offer overviews and drawings of p75NTR pathways.{{cite journal| pmid =16939974| year =2006| last1 =Reichardt| first1 =L. F.| title =Neurotrophin-regulated signalling pathways| journal =Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences| volume =361| issue =1473| pages =1545–64| doi =10.1098/rstb.2006.1894| pmc =1664664}}{{cite journal| pmid=15626491| year=2005| last1=Kalb| first1=R.| title=The protean actions of neurotrophins and their receptors on the life and death of neurons| journal=Trends in Neurosciences| volume=28| issue=1| pages=5–11| doi=10.1016/j.tins.2004.11.003| s2cid=8468230}}
External links
- {{MeshName|Nerve+Growth+Factor+Receptors}}
{{Growth factor receptors}}
{{Growth factor receptor modulators}}