This domain, primarily C-terminal, is found in a family of proteins thought to be involved in regulating gene activity in the proliferative and/or differentiative pathways induced by NGF [].
This family of phage proteins is functionally uncharacterised. The family includes bacteriophage Sf6 gene 66 () as well as phage N4 GP49 protein (). Proteins in this family are typically between 87 and 154 amino acids in length. There is a conserved NGF sequence motif.
This is the helical trans-membrane domain found in tumor necrosis factor receptor superfamily member 16 (also known as p75 neurotrophin receptor , and nerve growth factor receptor-NGFR). p75 plays prominent biological functions such the induction of cell death, and it demonstrates several other activities, like survival, axonal growth, and cell migration. The trans-membrane (TM) domain of p75 stabilizes the receptor dimers through a disulfide bond, essential for the NGF signalling Structural and mutational analysis indicate that Cys257 plays the key role in this stabilisation process. Furthermore, although the p75-C257A mutant is still capable to form dimers and bind to NGF, it is unable to transduce the signals triggered by NGF binding in some cell signalling paradigms [].
During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells []. Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF), which is involved in the survival of some classes of embryonic neuron (e.g., peripheral sympathetic neurons) []. NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown []; it has also been found in several snake venoms [, ]. Proteins similar to NGF include brain-derived neurotrophic factor (BDNF) and neurotrophins 3 to 7, all of which demonstrate neuron survival and outgrowth activities. Although NGF was originally identified in snake venom, its most abundant and best studied source is the submaxillary gland of adult male mice []. Mouse NGF is a high molecular weight hexamer, composed of 2 subunits each of alpha, beta and gamma polypeptides. The beta subunit (NGF-beta) is responsible for the physiological activity of the complex []. NGF-beta induces its cell survival effects through activation of neurotrophic tyrosine kinase receptor type 1 (NTRK1; also called TrkA), and can induce cell death by binding to the low affinity nerve growth factor receptor, p75NTR []. The neurotrophin has been shown to be involved in sympathetic axon growth and innervation of target fields [].
During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells []. Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF), which is involved in the survival of some classes of embryonic neuron (e.g., peripheral sympathetic neurons) []. NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown []; it has also been found in several snake venoms [, ]. Proteins similar to NGF include brain-derived neurotrophic factor (BDNF) and neurotrophins 3 to 7, all of which demonstrate neuron survival and outgrowth activities. Although NGF was originally identified in snake venom, its most abundant and best studied source is the submaxillary gland of adult male mice []. Mouse NGF is a high molecular weight hexamer, composed of 2 subunits each of alpha, beta and gamma polypeptides. The beta subunit (NGF-beta) is responsible for the physiological activity of the complex []. NGF-beta induces its cell survival effects through activation of neurotrophic tyrosine kinase receptor type 1 (NTRK1; also called TrkA), and can induce cell death by binding to the low affinity nerve growth factor receptor, p75NTR []. The neurotophin has been shown to be involved in sympathetic axon growth and innervation of target fields []. Mammalian NGF-beta tend to be higher potency NTRK1 agonsits than their snake venom counterparts []. In humans, NGF-beta gene mutations can cause a loss of pain perception [].
During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells []. Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF), which is involved in the survival of some classes of embryonic neuron (e.g., peripheral sympathetic neurons) []. NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown []; it has also been found in several snake venoms [, ]. Proteins similar to NGF include brain-derived neurotrophic factor (BDNF) and neurotrophins 3 to 7, all of which demonstrate neuron survival and outgrowth activities. This entry represents Neurotrophin-6 (NT-6), which has been identified in two species of platty fish []. It has been shown to have trophic effects on embryonic sympathetic neurons, similar to those of NGF [].
Smim3 (Small integral membrane protein 3) also known as NID67 (NGF-induced differentiation clone 67) may be involved in forming or regulating ion channels in neuronal differentiation. It is strongly induced by NGF (Nerve Growth Factor) and FGF (Fibroblast Growth Factor), both of which cause these cells to differentiate. The amino acid sequence of NID67 is strongly conserved among rat, mouse and human. This family of small membrane proteins is only 60 amino acids long and analysis of the predicted peptide sequence reveals a stretch of 29 hydrophobic and uncharged residues which very likely comprise a trans-membrane region [].
Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling []. They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains []. Vertebrates contain two APPL proteins, APPL1 and APPL2. APPL1 interacts with diverse receptors (e.g. NGF receptor TrkA, FSHR, adiponectin receptors) and signaling proteins (e.g. Akt, PI3K), and may function as an adaptor linked to many distinct signaling pathways []. This entry represents the BAR domain of APPL1.
During the development of the vertebrate nervous system, many neuronsbecome redundant (because they have died, failed to connect to targetcells, etc.) and are eliminated. At the same time, developing neurons sendout axon outgrowths that contact their target cells []. Such cells controltheir degree of innervation (the number of axon connections) by thesecretion of various specific neurotrophic factors that are essential forneuron survival. One of these is nerve growth factor (NGF or beta-NGF), a vertebrate protein that stimulatesdivision and differentiation of sympathetic and embryonic sensory neurons [,]. NGF is mostly found outside the centralnervous system (CNS), but slight traces have been detected in adult CNStissues, although a physiological role for this is unknown []; it has alsobeen found in several snake venoms [, ].NGF is a protein of about 120 residues that is cleaved from a largerprecursor molecule. It contains six cysteines all involved in intrachaindisulphide bonds. A schematic representation of the structure of NGF is shownbelow:+------------------------+| || |xxxxxxCxxxxxxxxxxxxxxxxxxxxxCxxxxCxxxxxCxxxxxxxxxxxxxCxCxxxx| | | |+--------------------------|-----+ |+---------------------+'C': conserved cysteine involved in a disulphide bond.This entry also contains NGF-related proteins such as neutrophin 3, which promotes the survival of visceral and proprioceptive sensory neurons, and brain-derived neurotrophin, which promotes the survival of neuronal populations that are located either in the central nervous system or directly connected to it [, ].
During the development of the vertebrate nervous system, many neuronsbecome redundant (because they have died, failed to connect to targetcells, etc.) and are eliminated. At the same time, developing neurons sendout axon outgrowths that contact their target cells []. Such cells controltheir degree of innervation (the number of axon connections) by thesecretion of various specific neurotrophic factors that are essential forneuron survival. One of these is nerve growth factor (NGF or beta-NGF), a vertebrate protein that stimulatesdivision and differentiation of sympathetic and embryonic sensory neurons [,]. NGF is mostly found outside the centralnervous system (CNS), but slight traces have been detected in adult CNStissues, although a physiological role for this is unknown []; it has alsobeen found in several snake venoms [, ].NGF is a protein of about 120 residues that is cleaved from a largerprecursor molecule. It contains six cysteines all involved in intrachaindisulphide bonds. A schematic representation of the structure of NGF is shownbelow:+------------------------+| || |xxxxxxCxxxxxxxxxxxxxxxxxxxxxCxxxxCxxxxxCxxxxxxxxxxxxxCxCxxxx| | | |+--------------------------|-----+ |+---------------------+'C': conserved cysteine involved in a disulphide bond.This entry also contains NGF-related proteins such as neutrophin 3, which promotes the survival of visceral and proprioceptive sensory neurons, and brain-derived neurotrophin, which promotes the survival of neuronal populations that are located either in the central nervous system or directly connected to it [, ].
During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells []. Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF), which is involved in the survival of some classes of embryonic neuron (e.g., peripheral sympathetic neurons) []. NGF is mostly found outsidethe central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown []; it has also been found in several snake venoms [, ]. Proteins similar to NGF include brain-derived neurotrophic factor (BDNF) and neurotrophins 3 to 7, all of which demonstrate neuron survival and outgrowth activities. Neurotrophin-4 (NT-4) exerts its effects by binding to neurotrophic tyrosine kinase receptor type 2 (NTRK2; also called TrkB). NT-4 has been shown to play a crucial role in the development of long-term memory []. It has also been implicated in the regulation of appetite and in body weight control [].
During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells []. Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF or beta-NGF), a vertebrate protein that stimulates division and differentiation of sympathetic and embryonic sensory neurons [, ]. NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown []; it has also been found in several snake venoms [, ].NGF is a protein of about 120 residues that is cleaved from a larger precursor molecule. It contains six cysteines all involved in intrachain disulphide bonds.Neurotrophin-3 is a neurotrophic factor related to NGF and BDNF []. NT-3 and its receptor TrkC are found in the spinal cord, and their expression is altered by voluntary exercise [, , ]. In the brain, NT-3 and NT-4/5 may function synergistically with oleic acid to increase GAP-43 expression [].
During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells []. Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF), which is involved in the survival of some classes of embryonic neuron (e.g., peripheral sympathetic neurons) []. NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown []; it has also been found in several snake venoms [, ]. Proteins similar to NGF include brain-derived neurotrophic factor (BDNF) and neurotrophins 3 to 7, all of which demonstrate neuron survival andoutgrowth activities. In contrast to mammalian NGFs, which exist as multimeric complexes of alpha, beta and gamma subunits, snake venom NGFs exist almost exclusively as beta-chains []. They act as low-potency neurotrophic tyrosine kinase receptor type 1 (NTRK1; also called TrkA) agonists [], and have been shown to promote survival and differentiation of cultured cells [].
During the development of the vertebrate nervous system, many neuronsbecome redundant (because they have died, failed to connect to targetcells, etc.) and are eliminated. At the same time, developing neurons sendout axon outgrowths that contact their target cells []. Such cells controltheir degree of innervation (the number of axon connections) by thesecretion of various specific neurotrophic factors that are essential forneuron survival. One of these is nerve growth factor (NGF or beta-NGF), a vertebrate protein that stimulatesdivision and differentiation of sympathetic and embryonic sensory neurons [,]. NGF is mostly found outside the centralnervous system (CNS), but slight traces have been detected in adult CNStissues, although a physiological rolefor this is unknown []; it has alsobeen found in several snake venoms [, ].NGF is a protein of about 120 residues that is cleaved from a largerprecursor molecule. It contains six cysteines all involved in intrachaindisulphide bonds. A schematic representation of the structure of NGF is shownbelow:+------------------------+| || |xxxxxxCxxxxxxxxxxxxxxxxxxxxxCxxxxCxxxxxCxxxxxxxxxxxxxCxCxxxx| | | |+--------------------------|-----+ |+---------------------+'C': conserved cysteine involved in a disulphide bond.This entry also contains NGF-related proteins such as neutrophin 3, which promotes the survival of visceral and proprioceptive sensory neurons, and brain-derived neurotrophin, which promotes the survival of neuronal populations that are located either in the central nervous system or directly connected to it [, ].This entry covers the central region of the proteins and include two of the six cysteines involved in disulphide bonds.
During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells []. Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF), which is involved in the survival of some classes of embryonic neuron (e.g., peripheral sympathetic neurons) []. NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown []; it has also been found in several snake venoms [, ]. Proteins similar to NGF include brain-derived neurotrophic factor (BDNF) and neurotrophins 3 to 7, all of which demonstrate neuron survival and outgrowth activities. Originally purified from pig brain [], the neurotrophin BDNF is expressed in a range of tissues and cell types in the CNS and periphery. It exerts its effects by binding to neurotrophic tyrosine kinase receptor type 2 (NTRK2; also called TrkB) and the low affinity nerve growth factor receptor, p75NTR. While the former receptor mediates the neurotrophin's prosurvival functions, activation of p75NTR by BDNF has been shown to promote apoptosis and to inhibit axonal growth []. BDNF is a key regulator of synaptic plasticity, and plays an important role in learning and memory []. Several lines of evidence suggest that it is also involved in the control of food intake and body weight []. A number of clinical studies have demonstrated an association between aberrant BDNF levels and disorders and disease states, such as depression, epilepsy, bipolar disorder, Parkinson's disease and Alzheimer's disease [].
Neurotrophins are a family of secreted proteins that regulate development, maintenance and function of vertebrate nervous systems. They act via two different classes of receptor: p75NTR (a member of the TNF receptor superfamily), and neurotrophic tyrosine kinase receptors (NTRKs) - also known as tropomyosin-related kinases (Trks) []. NTRKs are multi-domain, transmembrane proteins - in addition to their cytoplasmic kinase domains, members of the family possess a number of extracellular leucine-rich repeat (LRR) and Ig-like C2-type regions. Ligand binding induces them to dimerise, resulting in activation of their cytoplasmic tyrosine kinase domains. The activated receptors couple to a variety of intracellular signalling cascades, including the Ras, phosphatidylinositol-3-kinase (PI-3 kinase), mitogen-activated protein (MAP) kinase, and phospholipase C (PLC)-gamma pathways []. NTRK1 (also termed TrkA) is a high-affinity receptor for nerve growth factor (NGF). The receptor is expressed in the dorsal root ganglia, trigeminal ganglia and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons []. It is also expressed in peripheral sites, such as scalp skin []. Whereas p75NTR activation by NGF induces apoptosis, NTRK1 mediates the growth factor's cell survival-promoting effects [].
Tumor necrosis factor receptor superfamily member 16 (TNFRSF16), also known as nerve growth factor receptor (NGFR) or p75 neurotrophin receptor (p75NTR or p75), CD271, or Gp80-LNGFR, is a common receptor for both neurotrophins and proneurotrophins, and plays a diverse role in many tissues, including the nervous system. It has been shown to be expressed in various types of stem cells and has been used to prospectively isolate stem cells with different degrees of potency []. p75NTR owes its signaling to the recruitment of intracellular binding proteins, leading to the activation of different signaling pathways []. It binds nerve growth factor (NGF) and the complex can initiate a signaling cascade which has been associated with both neuronal apoptosis and neuronal survival of discrete populations of neurons, depending on the presence or absence of intracellular signaling molecules downstream of p75NTR (e.g. NF-kB, JNK, or p75NTR intracellular death domain). p75NTR can also bind NGF in concert with the neurotrophic tyrosine kinase receptor type 1 (TrkA) protein where it is thought to modulate the formation of the high-affinity neurotrophin binding complex [].In melanoma cells, p75NTR is an immunosuppressive factor, induced by interferon (IFN)-gamma, and mediates down-regulation of melanoma antigens []. It can interact with the aggregated form of amyloid beta (Abeta) peptides, and plays an important role in etiopathogenesis of Alzheimer's disease by influencing protein tau hyper-phosphorylation []. p75NTR is involved in the formation and progression of retina diseases; its expression is induced in retinal pigment epithelium (RPE) cells and its knockdown rescues RPE cell proliferation activity and inhibits RPE apoptosis induced by hypoxia []. It can therefore be a potential therapeutic target for RPE hypoxia or oxidative stress diseases.This entry represents the N-terminal domain of TNFRSF16. TNF-receptors are modular proteins. The N-terminal extracellular part contains a cysteine-rich region responsible for ligand-binding. This region is composed of small modules of about 40 residues containing 6 conserved cysteines; the number and type of modules can vary in different members of the family [, , ].
