Low Affinity Nerve Growth Factor Receptor
Encyclopedia
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
(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 that are capable of responding to this growth factor, TrkA
and the LNGFR.
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 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.
with PRKACB
, FSCN1
, TRAF4
, Nerve growth factor
, TRAF2
, NDN
, NGFRAP1
and MAGEH1
.
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
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
TrkA
High affinity nerve growth factor receptor also known as neurotrophic tyrosine kinase receptor type 1 or TRK1-transforming tyrosine kinase protein or Trk-A is a protein that in humans is encoded by the NTRK1 gene....
.
The Neurotrophins
The neurotrophins are composed of four proteins, all of which bind to the LNGFR:Nerve Growth Factor
Nerve growth factor
Nerve growth factor is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons . It also functions as a signaling molecule. It is perhaps the prototypical growth factor, in that it is one of the first to be described...
(NGF), Brain Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3), and Neurotrophin-4 (NT-4
NT-4
Neurotrophin-4 , also known as neurotrophin-5 , is a protein that in humans is encoded by the NTF4 gene.NT-4 is a neurotrophic factor that signals predominantly through the TrkB receptor tyrosine kinase....
).
Nerve growth factor
Nerve growth factor
Nerve growth factor is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons . It also functions as a signaling molecule. It is perhaps the prototypical growth factor, in that it is one of the first to be described...
, 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
NGF
NGF may refer to:*Nerve growth factor*Naval gunfire*Northern Group of Forces*National Golf Foundation*North German Federation...
is released from the target cells, binds to and activates its high-affinity receptor (TrkA
TrkA
High affinity nerve growth factor receptor also known as neurotrophic tyrosine kinase receptor type 1 or TRK1-transforming tyrosine kinase protein or Trk-A is a protein that in humans is encoded by the NTRK1 gene....
), and is internalized into the responsive neuron. The NGF
NGF
NGF may refer to:*Nerve growth factor*Naval gunfire*Northern Group of Forces*National Golf Foundation*North German Federation...
/TrkA
TrkA
High affinity nerve growth factor receptor also known as neurotrophic tyrosine kinase receptor type 1 or TRK1-transforming tyrosine kinase protein or Trk-A is a protein that in humans is encoded by the NTRK1 gene....
complex is subsequently trafficked back to the cell body. This movement of NGF
NGF
NGF may refer to:*Nerve growth factor*Naval gunfire*Northern Group of Forces*National Golf Foundation*North German Federation...
from axon tip to soma is thought to be involved in the long-distance signaling of neurons.
The activation of TrkA
TrkA
High affinity nerve growth factor receptor also known as neurotrophic tyrosine kinase receptor type 1 or TRK1-transforming tyrosine kinase protein or Trk-A is a protein that in humans is encoded by the NTRK1 gene....
by NGF
NGF
NGF may refer to:*Nerve growth factor*Naval gunfire*Northern Group of Forces*National Golf Foundation*North German Federation...
is critical in inducing the survival and differentiation caused by this growth factor.
However, NGF
NGF
NGF may refer to:*Nerve growth factor*Naval gunfire*Northern Group of Forces*National Golf Foundation*North German Federation...
binds at least two receptors on the surface of cells that are capable of responding to this growth factor, TrkA
TrkA
High affinity nerve growth factor receptor also known as neurotrophic tyrosine kinase receptor type 1 or TRK1-transforming tyrosine kinase protein or Trk-A is a protein that in humans is encoded by the NTRK1 gene....
and the LNGFR.
The Trk family of receptor tyrosine kinases
TrkATrkA
High affinity nerve growth factor receptor also known as neurotrophic tyrosine kinase receptor type 1 or TRK1-transforming tyrosine kinase protein or Trk-A is a protein that in humans is encoded by the NTRK1 gene....
is a receptor tyrosine kinase
Receptor tyrosine kinase
Receptor tyrosine kinases s are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins....
(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
TrkB
TrkB receptor also known as TrkB tyrosine kinase 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.-Function:...
and TrkC
TrkC
NT-3 growth factor receptor also known as neurotrophic tyrosine kinase receptor type 3 or TrkC tyrosine kinase or Trk-C receptor is a protein that in humans is encoded by the NTRK3 gene....
. 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
TrkA
High affinity nerve growth factor receptor also known as neurotrophic tyrosine kinase receptor type 1 or TRK1-transforming tyrosine kinase protein or Trk-A is a protein that in humans is encoded by the NTRK1 gene....
mediates the effects of NGF
NGF
NGF may refer to:*Nerve growth factor*Naval gunfire*Northern Group of Forces*National Golf Foundation*North German Federation...
, TrkB
TrkB
TrkB receptor also known as TrkB tyrosine kinase 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.-Function:...
binds and is activated by BDNF, NT-4, and NT-3, and TrkC
TrkC
NT-3 growth factor receptor also known as neurotrophic tyrosine kinase receptor type 3 or TrkC tyrosine kinase or Trk-C receptor is a protein that in humans is encoded by the NTRK3 gene....
binds and is activated only by NT-3.
The role of the LNGFR
As opposed to TrkATrkA
High affinity nerve growth factor receptor also known as neurotrophic tyrosine kinase receptor type 1 or TRK1-transforming tyrosine kinase protein or Trk-A is a protein that in humans is encoded by the NTRK1 gene....
, 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
TrkA
High affinity nerve growth factor receptor also known as neurotrophic tyrosine kinase receptor type 1 or TRK1-transforming tyrosine kinase protein or Trk-A is a protein that in humans is encoded by the NTRK1 gene....
, 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.
Interactions
Low-affinity nerve growth factor receptor has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with PRKACB
PRKACB
cAMP-dependent protein kinase catalytic subunit beta is an enzyme that in humans is encoded by the PRKACB gene.-Interactions:PRKACB has been shown to interact with Ryanodine receptor 2 and Low affinity nerve growth factor receptor.-Further reading:...
, FSCN1
FSCN1
Fascin is a protein that in humans is encoded by the FSCN1 gene.-Interactions:FSCN1 has been shown to interact with Low affinity nerve growth factor receptor and PKC alpha.-Further reading:...
, TRAF4
TRAF4
TNF receptor-associated factor 4 also known as RING finger protein 83 is a protein that in humans is encoded by the TRAF4 gene.TRAF4 is a member of the TNF receptor associated factor family, a family of scaffold proteins...
, Nerve growth factor
Nerve growth factor
Nerve growth factor is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons . It also functions as a signaling molecule. It is perhaps the prototypical growth factor, in that it is one of the first to be described...
, TRAF2
TRAF2
TNF receptor-associated factor 2 is a protein that in humans is encoded by the TRAF2 gene.-Interactions:TRAF2 has been shown to interact with BCL10, CD30, CFLAR, IKK2, MAP3K7IP2, CD137, Caveolin 1, CD27, TNFRSF13B, TANK-binding kinase 1, TRAF1, CD40, UBE2N, MAP3K14, MAP4K2, CASP8AP2, HIVEP3,...
, NDN
NDN (gene)
Necdin is a protein that in humans is encoded by the NDN gene.-Interactions:NDN has been shown to interact with NUCB2, E2F1, IL1A, Low affinity nerve growth factor receptor, P53 and HNRNPU.-Further reading:...
, NGFRAP1
NGFRAP1
Protein BEX3 is a protein that in humans is encoded by the NGFRAP1 gene.-Interactions:NGFRAP1 has been shown to interact with YWHAE and Low affinity nerve growth factor receptor.-Further reading:...
and MAGEH1
MAGEH1
Melanoma-associated antigen H1 is a protein that in humans is encoded by the MAGEH1 gene.-Interactions:MAGEH1 has been shown to interact with Low affinity nerve growth factor receptor.-Further reading:...
.