Neurotrophic factor receptors or neurotrophin receptors are a group of
growth factor receptor
A growth factor receptor is a receptor that binds to a growth factor. Growth factor receptors are the first stop in cells where the signaling cascade for cell differentiation and proliferation begins. Growth factors, which are ligands that bind to ...
s which specifically bind to
neurotrophins (neurotrophic factors).
Two classes of neurotrophic factor receptors are the p75 and the "Trk" families of
Tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.
Tyrosine kinases belong to a larger cla ...
s 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.
* The
Trk family include
TrkA
Tropomyosin receptor kinase A (TrkA), also known as high affinity nerve growth factor receptor, neurotrophic tyrosine kinase receptor type 1, or TRK1-transforming tyrosine kinase protein is a protein that in humans is encoded by the ''NTRK1'' gen ...
,
TrkB
Tropomyosin receptor kinase B (TrkB), also known as tyrosine receptor kinase B, or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the ''NTRK2'' gene. TrkB is a recepto ...
, and
TrkC
Tropomyosin receptor kinase C (TrkC), also known as NT-3 growth factor receptor, neurotrophic tyrosine kinase receptor type 3, or TrkC tyrosine kinase is a protein that in humans is encoded by the ''NTRK3'' gene.
TrkC is the high affinity catalyt ...
, 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
Tropomyosin receptor kinase C (TrkC), also known as NT-3 growth factor receptor, neurotrophic tyrosine kinase receptor type 3, or TrkC tyrosine kinase is a protein that in humans is encoded by the ''NTRK3'' gene.
TrkC is the high affinity catalyt ...
. 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
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
.
TrkA, B, and C receptors
TrkA
Tropomyosin receptor kinase A (TrkA), also known as high affinity nerve growth factor receptor, neurotrophic tyrosine kinase receptor type 1, or TRK1-transforming tyrosine kinase protein is a protein that in humans is encoded by the ''NTRK1'' gen ...
mediates its actions by causing the addition of
phosphate
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid .
The phosphate or orthophosphate ion is derived from phospho ...
molecules on certain tyrosines in the cell, activating cellular signaling.
There are other related Trk receptors (
TrkB
Tropomyosin receptor kinase B (TrkB), also known as tyrosine receptor kinase B, or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the ''NTRK2'' gene. TrkB is a recepto ...
and
TrkC
Tropomyosin receptor kinase C (TrkC), also known as NT-3 growth factor receptor, neurotrophic tyrosine kinase receptor type 3, or TrkC tyrosine kinase is a protein that in humans is encoded by the ''NTRK3'' gene.
TrkC is the high affinity catalyt ...
), and there are other neurotrophic factors structurally related to NGF (
BDNF
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the cano ...
,
NT-3
Neurotrophin-3 is a protein that in humans is encoded by the ''NTF3'' gene.
The protein encoded by this gene, NT-3, is a neurotrophic factor in the NGF (Nerve Growth Factor) family of neurotrophins. It is a protein growth factor which has activ ...
, and
NT-4
Neurotrophin-4 (NT-4), also known as neurotrophin-5 (NT-5), is a protein that in humans is encoded by the ''NTF4'' gene. It is a neurotrophic factor that signals predominantly through the TrkB receptor tyrosine kinase
Receptor tyrosine kinase ...
)
*
TrkA
Tropomyosin receptor kinase A (TrkA), also known as high affinity nerve growth factor receptor, neurotrophic tyrosine kinase receptor type 1, or TRK1-transforming tyrosine kinase protein is a protein that in humans is encoded by the ''NTRK1'' gen ...
mediates the effects of NGF
*
TrkB
Tropomyosin receptor kinase B (TrkB), also known as tyrosine receptor kinase B, or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the ''NTRK2'' gene. TrkB is a recepto ...
binds and is activated by
BDNF
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the cano ...
,
NT-4
Neurotrophin-4 (NT-4), also known as neurotrophin-5 (NT-5), is a protein that in humans is encoded by the ''NTF4'' gene. It is a neurotrophic factor that signals predominantly through the TrkB receptor tyrosine kinase
Receptor tyrosine kinase ...
, and
NT-3
Neurotrophin-3 is a protein that in humans is encoded by the ''NTF3'' gene.
The protein encoded by this gene, NT-3, is a neurotrophic factor in the NGF (Nerve Growth Factor) family of neurotrophins. It is a protein growth factor which has activ ...
*
TrkC
Tropomyosin receptor kinase C (TrkC), also known as NT-3 growth factor receptor, neurotrophic tyrosine kinase receptor type 3, or TrkC tyrosine kinase is a protein that in humans is encoded by the ''NTRK3'' gene.
TrkC is the high affinity catalyt ...
binds and is activated only by
NT-3
Neurotrophin-3 is a protein that in humans is encoded by the ''NTF3'' gene.
The protein encoded by this gene, NT-3, is a neurotrophic factor in the NGF (Nerve Growth Factor) family of neurotrophins. It is a protein growth factor which has activ ...
p75NTR receptor
The
Low affinity nerve growth factor receptor
The p75 neurotrophin receptor (p75NTR) was first identified in 1973 as the low-affinity nerve growth factor receptor (LNGFR) before discovery that p75NTR bound other neurotrophins equally well as nerve growth factor. p75NTR is a neurotrophic facto ...
commonly known as "p75", can signal for apoptosis or promote neuronal survival.
Neurotrophins that interact with p75NTR include
NGF,
NT-3
Neurotrophin-3 is a protein that in humans is encoded by the ''NTF3'' gene.
The protein encoded by this gene, NT-3, is a neurotrophic factor in the NGF (Nerve Growth Factor) family of neurotrophins. It is a protein growth factor which has activ ...
,
BDNF
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the cano ...
, and
NT-4/5. Neurotrophins activating p75NTR may initiate
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
(for example, via
c-Jun N-terminal kinases
c-Jun N-terminal kinases (JNKs), were originally identified as kinases that bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. They belong to the mitogen-activated protein kinase family, and are res ...
signaling), and this effect can be counteracted by anti-apoptotic signaling by
TrkA
Tropomyosin receptor kinase A (TrkA), also known as high affinity nerve growth factor receptor, neurotrophic tyrosine kinase receptor type 1, or TRK1-transforming tyrosine kinase protein is a protein that in humans is encoded by the ''NTRK1'' gen ...
. Neurotrophin binding to p75NTR can promote neuronal survival (for example, via
NF-kB activation).
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
The p75 neurotrophin receptor (p75NTR) was first identified in 1973 as the low-affinity nerve growth factor receptor (LNGFR) before discovery that p75NTR bound other neurotrophins equally well as nerve growth factor. p75NTR is a neurotrophic fact ...
and negative for
TrkA
Tropomyosin receptor kinase A (TrkA), also known as high affinity nerve growth factor receptor, neurotrophic tyrosine kinase receptor type 1, or TRK1-transforming tyrosine kinase protein is a protein that in humans is encoded by the ''NTRK1'' gen ...
.
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
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
death in a variety of neurodegenerative conditions, including
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
, following the observation of an increase of proNGF in the
nucleus
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
*Atomic nucleus, the very dense central region of an atom
*Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucle ...
basalis of postmortem Alzheimer's brains .
References
Further reading
Review papers offer overviews and drawings of p75NTR pathways.
External links
*
{{Growth factor receptor modulators
Receptors
Single-pass transmembrane proteins