Neurotrophin-3
Encyclopedia
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 activity on certain neuron
s of the peripheral and central nervous system
; it helps to support the survival and differentiation of existing neurons, and encourages the growth and differentiation of new neurons and synapse
s. NT-3 was the third neurotrophic factor to be characterized, after nerve growth factor
(NGF
) and BDNF (Brain Derived Neurotrophic Factor).
ian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cell
s; a process known as neurogenesis
. Neurotrophins are chemicals that help to stimulate and control neurogenesis.
NT-3 is unique in the number of neurons it can potentially stimulate, given its ability to activate two of the receptor tyrosine kinase neurotrophin receptors (TrkC
and TrkB
- see below).
Mice born without the ability to make NT-3 have loss of proprioceptive and subsets of mechanoreceptive sensory neurons.
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).
As mentioned above, there are other related Trk receptors, TrkA
and TrkB
. Also as mentioned, there are other neurotrophic factors structurally related to NT-3:
While TrkB mediates the effects of BDNF, NT-4, and NT-3, TrkA
binds and is activated by NGF
, and TrkC binds and is activated only by NT-3.
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 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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the NTF3 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
The protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
encoded by this gene, NT-3, is a neurotrophic factor in the NGF (Nerve Growth Factor) family of neurotrophins. It is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
which has activity on certain neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s of the peripheral and central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
; it helps to support the survival and differentiation of existing neurons, and encourages the growth and differentiation of new neurons and synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
s. NT-3 was the third neurotrophic factor to be characterized, after 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
NGF
NGF may refer to:*Nerve growth factor*Naval gunfire*Northern Group of Forces*National Golf Foundation*North German Federation...
) and BDNF (Brain Derived Neurotrophic Factor).
Function
Although the vast majority of neurons in the mammalMammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
s; a process known as neurogenesis
Neurogenesis
Neurogenesis is the process by which neurons are generated from neural stem and progenitor cells. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain with neurons. Recently neurogenesis was shown to continue in several small parts of the brain of...
. Neurotrophins are chemicals that help to stimulate and control neurogenesis.
NT-3 is unique in the number of neurons it can potentially stimulate, given its ability to activate two of the receptor tyrosine kinase neurotrophin receptors (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....
and 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:...
- see below).
Mice born without the ability to make NT-3 have loss of proprioceptive and subsets of mechanoreceptive sensory neurons.
Mechanism of action
NT-3 binds three receptors on the surface of cells which are capable of responding to this growth factor:- TrkCTrkCNT-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....
, is apparently the "physiologic" receptor, in that it binds with greatest affinity to NT-3.
- However, NT-3 is capable of binding and signaling through a TrkC-related receptors called TrkBTrkBTrkB 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:...
.
- Finally, NT-3 also binds a second-receptor type besides Trk receptors, called the LNGFR (for "low affinity nerve growth factor receptor).
High affinity receptors
TrkCTrkC
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....
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).
As mentioned above, there are other related Trk receptors, 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 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:...
. Also as mentioned, there are other neurotrophic factors structurally related to NT-3:
- NGFNerve growth factorNerve 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...
(for "Nerve Growth Factor") - BDNF (for "Brain Derived Neurotrophic Factor")
- NT-4NT-4Neurotrophin-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....
(for "Neurotrophin-4")
While TrkB mediates the effects of BDNF, NT-4, and NT-3, 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....
binds and is activated by NGF
NGF
NGF may refer to:*Nerve growth factor*Naval gunfire*Northern Group of Forces*National Golf Foundation*North German Federation...
, and TrkC binds and is activated only by NT-3.
Low affinity receptors
The other NT-3 receptor, the LNGFR, plays a somewhat less clear role. 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 the LNGFR may signal a cell to die via apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
- so therefore cells expressing the LNGFR in the absence of Trk receptors may die rather than live in the presence of a neurotrophin.