Cloning and expression of a cDNA encoding a novel human neurotrophic factor

Kaisho, Yoshihiko; Yoshimura, Koji; Nakahama, Kazuo

doi:10.1016/0014-5793(90)81536-w

Cited by 192 publications

(65 citation statements)

References 19 publications

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“…Different members ofthe neurotrophin family [nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) (Leibrock et al, 1989) neurotrophin-3 (NT-3) (Hohn et al, 1990;Kaisho et al, 1990;Maisonpierre et al, 1990;Rosenthal et al, 1990), and neurotrophin 4/5 (NT-4/5) (Berkemeier et al, 1991;Hallbook et al, 1991;Ip et al, 1992)] exhibit actions on distinct, but overlapping, sets of peripheral and central neurons. These effects range from playing a crucial role in ensuring the survival of developing neurons (NGF in sensory and sympathetic neurons) (Levi-Montalcini and Booker, 1960) to relatively subtle effects on the morphology of neurons (NT-3 on Purkinje cells) (Lindholm et al, 1993).…”

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confidence: 99%

Human trks: molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesins

Shelton¹,

Sutherland²,

Gripp³

et al. 1995

J. Neurosci.

365

282

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Using molecular cloning techniques, human homologs of the known members of the trk family of neurotrophin receptors have been cloned and sequenced. Overall, there is a high degree of similarity between the human sequences and those from other mammals; however, there are differences in splicing patterns. There are two spliced forms of the extracellular domain of trkC in the human, a finding that has not been described in other species. In contrast, fewer spliced forms were detected of the intracellular domains of human trkB and trkC than has been described in other mammals. Northern analysis and in situ hybridization experiments indicate that the human trks are expressed in a similar pattern to that described in other mammals. Expression of the trk extracellular domains as fusion proteins with IgG heavy chain yields soluble molecules that mimic intact trks in their binding specificity and affinity. These soluble chimeras block the biological activity of their cognate neurotrophin(s) in vitro.

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confidence: 99%

Human trks: molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesins

Shelton¹,

Sutherland²,

Gripp³

et al. 1995

J. Neurosci.

365

282

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“…The neurotrophins are structurally and functionally related neurotrophic factors that function in the developing and adult nervous system (1)(2)(3). In mammals, the neurotrophin family presently includes four members, nerve growth factor (NGF) 1 (4), brainderived neurotrophic factor (BDNF) (5,6), neurotrophin-3 (NT-3) (7)(8)(9)(10)(11)(12), and neurotrophin-4 (NT-4) (13,14), also called NT-5 (15), which share approximately 50% amino acid sequence identity. An additional neurotrophin molecule with structural and functional similarities to NGF has recently been isolated from the platty fish and named , despite being only the third neurotrophin identified in this species.…”

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confidence: 99%

Binding of Neurotrophin-3 to p75LNGFR, TrkA, and TrkB Mediated by a Single Functional Epitope Distinct from That Recognized by TrkC

Rydén

Ibáñez

1996

Journal of Biological Chemistry

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Neurotrophins regulate differentiation and survival of vertebrate neurons through binding to members of the Trk family of receptor tyrosine kinases and to a common low affinity receptor, p75 LNGFR. The specificity of neurotrophin action is determined by their selective interaction with the different members of the Trk family; TrkA, TrkB, and TrkC serve as cognate receptors for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 (NT-3), respectively. Unlike nerve growth factor and brain-derived neurotrophic factor, NT-3 can to some extent also bind and activate noncognate TrkA and B receptors, although the physiological relevance of these interactions is unclear. Previous studies established that neurotrophins use an extended surface for binding to cognate Trk receptors, while binding to p75LNGFR is mediated by a localized cluster of positively charged residues. Here we show that the binding site of NT-3 to its non-preferred receptors TrkA and TrkB is dominated by two positively charged residues, Arg-31 and His-33, previously shown to constitute a main determinant of binding to p75 LNGFR. Simultaneous mutation of these two residues into Ala completely abolished NT-3 binding and signaling through TrkA and greatly diminished binding and activation of TrkB. However, NT-3 binding and signaling through its cognate receptor TrkC was unaffected by the mutation. These results show that binding of NT-3 to p75 LNGFR , TrkA, and TrkB is mediated by a common determinant, which is distinct from that recognized by TrkC and also different and more localized than the one recognized by TrkA and TrkB in their cognate ligands. Thus, although homologous regions in all neurotrophins are used for binding to Trk receptors, a given Trk may actually contact different residues in different neurotrophins. The mutant NT-3 described here may be of greater advantage than native NT-3 when a trophic activity needs to be specifically targeted to TrkC-expressing neurons and provides a monospecific neurotrophin for future therapeutic development.Vertebrate neurons are dependent on the continuous supply of a group of proteins generally called neurotrophic factors for their development, differentiation, and survival. The neurotrophins are structurally and functionally related neurotrophic factors that function in the developing and adult nervous system (1-3). In mammals, the neurotrophin family presently includes four members, nerve growth factor (NGF) 1 (4), brainderived neurotrophic factor (BDNF) (5, 6), neurotrophin-3 (NT-3) (7-12), and neurotrophin-4 (NT-4) (13, 14), also called NT-5 (15), which share approximately 50% amino acid sequence identity. An additional neurotrophin molecule with structural and functional similarities to NGF has recently been isolated from the platty fish and named NT-6 (16), despite being only the third neurotrophin identified in this species. The neurotrophins are non-covalently linked homodimers of two highly basic 120-residue long polypeptide chains. Each protomer contains three disulfide brid...

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“…During the last years much interest has been focused on NGF (13), the first member of a family of structurally related neurotrophic factors including brain-derived neurotrophic factor (BDNF) (14,15), neurotrophin 3 (NT3; also called hippocampus-derived neurotrophic factor) (16)(17)(18)(19)(20), and neurotrophin 4 (21). NGF, BDNF, and NT3 are all expressed in the brain (16,20,(22)(23)(24)(25)(26)(27).…”

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confidence: 99%

Expanded distribution of mRNA for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the rat brain after colchicine treatment.

Ceccatelli

Ernfors

Villar

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

108

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The effect of intracerebroventricular iqjection of the mitosis inhibitor colchicine on expression of mRNA for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 was studied in the rat brain with in situ hybridization. Colchicine up-regulates mRNA for NGF and BDNF in many of the neuronal systems normally expressing these factors. In addition, after colchicine treatment NGF and BDNF mRNAs were localized in several brain areas where they normally cannot be detected. Thus, NGF mRNA was present, for example, in many motor nuclei and in the basal forebrain, and BDNF mRNA was seen in many nuclei in the brain stem and in catecholamine neurons, including dopame neurons in the substantia nigra. The latter neurons have recently been shown to be sensitive to BDNF, and the present results show that these neurons can produce this factor themselves. A decrease in mRNA for BDNF and neurotrophin 3 was seen only in the granular-cell layer of the hippocampal formation. A strong hybridization sgnal for BDNF and neurotrophin 3 mRNA was also observed over several myelinated tracts in treated rats, supporting the hypothesis that glial cells as well as neurons can produce these trophic factors.The antimitotic agent colchicine is known to inhibit axonal transport of neuroactive-compounds (1, 2) and to cause accumulation of transmitter-storage vesicles in cell somata (3). Subsequently colchicine has frequently been used in immunohistochemical studies to increase levels of transmitters, peptides, and related substances in cell bodies (4, 5). Colchicine arrests axonal transport due to microtubule disruption (6). However, it has been assumed that protein/ peptide synthesis remains unaffected, leading to accumulation of various compounds in the cell bodies.More recently colchicine has been shown to have a more complex action on neurons. For example, colchicine increases c-Fos levels in many brain areas (7) and causes changes in mRNA levels for a number of peptides, enzymes, and other substances (8). For instance, in the cholinergic basal forebrain system mRNA levels for choline acetyltransferase (acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6) are lowered, whereas mRNA levels for the peptide galanin are dramatically increased in this and many other systems (8).A similar up-regulation of galanin mRNA levels in basal forebrain neurons occurs after an electrolytic lesion of the hippocampus (9). In other systems it has been proposed that proteins up-regulated after lesions may be needed for restitution and survival and that transmitter-related compounds may be down-regulated (10). For example, the low-affinity 75-kDa nerve growth factor (NGF) receptor is up-regulated in motoneurons after axotomy (11) and after intracerebroventricular injection of colchicine (12).During the last years much interest has been focused on NGF (13), the first member of a family of structurally related neurotrophic factors including brain-derived neurotrophic factor (BDNF) (14, 15), neurotrophin 3 (NT3; also called hippo...

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Cloning and expression of a cDNA encoding a novel human neurotrophic factor

Cited by 192 publications

References 19 publications

Human trks: molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesins

Human trks: molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesins

Binding of Neurotrophin-3 to p75LNGFR, TrkA, and TrkB Mediated by a Single Functional Epitope Distinct from That Recognized by TrkC

Expanded distribution of mRNA for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the rat brain after colchicine treatment.

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