Other entities represented in this entry:
HGNC Approved Gene Symbol: VGF
Cytogenetic location: 7q22.1 Genomic coordinates (GRCh38): 7:101,162,509-101,169,952 (from NCBI)
The nonacronym 'Vgf8a,' or Vgf, is the name given by Levi et al. (1985) to a gene discovered in the PC12 rat pheochromocytoma cell line upon activation of those cells to a neuronal phenotype by nerve growth factor (NGF; 162030). Levi et al. (1985) cloned rat Vgf8a.
Canu et al. (1997) noted that rat Vgf encodes a predicted 70-kD polypeptide that shares similarities with the secretogranin/chromogranin family (see 118920) and is found in the secretory granules of subsets of neurons and endocrine cells. Expression of Vgf is developmentally regulated. In the adult animal, both the mRNA and the protein levels are regulated in different areas of the brain in response to different stimuli (for review, see Ferri and Possenti (1996)). Canu et al. (1997) cloned human VGF, which encodes a deduced 616-amino acid protein containing a 22-amino acid signal sequence. Northern blot analysis of human tissues detected a VGF transcript of 2.7 kb in brain only.
Bartolomucci et al. (2006) stated that rat Vgf encodes a 617-amino acid precursor protein that is processed into shorter neuropeptides. TLQP-62, which is named after its first 4 amino acids and total number of residues, is a major Vgf peptide in the rat central nervous system. Bartolomucci et al. (2006) identified another rat peptide, TLQP-21, that originates from the same region of the Vgf precursor as TLQP-62.
By mass spectrometric analysis of C-terminally amidated peptides secreted from a human medullary thyroid carcinoma cell line, Yamaguchi et al. (2007) identified NERP1 and NERP2. The 26- and 38-amino acid peptides have molecular masses of 2.7 and 4.1 kD and are derived from VGF residues 281 to 306 and 310 to 347, respectively. Both peptides were amidated prior to secretion. Yamaguchi et al. (2007) found that rat Nerp1 and Nerp2, which contain 25 and 38 amino acids, respectively, were highly expressed in rat hypothalamus. Immunohistochemical analysis detected the rat peptides in supraoptic nuclei (SON) and in both the magnocellular and parvocellular divisions of paraventricular nuclei (PVN). Immunogold electron microscopy revealed colocalization of rat Nerps with vasopressin (AVP; 192340) in storage granules, but the Nerps rarely colocalized with oxytocin (OXT; 167050).
Levi et al. (1985) determined the dose-response curve for induction of rat Vgf8a by NGF. Canu et al. (1997) noted that rat Vgf is also regulated by brain-derived neurotrophic factor (BDNF; 113505) and neurotrophin-3 (NTF3; 162660) in primary cultures of cortical or hippocampal neurons (for review, see Ferri and Possenti (1996)).
Bartolomucci et al. (2006) showed that chronic intracerebroventricular injection of TLQP-21 increased resting energy expenditure and rectal temperature in mice. These effects were paralleled by increased epinephrine and upregulation of beta-1 adrenergic receptor (ADRB1; 109630) in brown adipose tissue and Ppar-delta (PPARD; 600409), Adrb3 (109691), and uncoupling protein-1 (UCP1; 113730) in white adipose tissue. In mice fed a high-fat diet, TLQP-21 prevented increases in body and white adipose tissue weights, as well as hormonal changes associated with a high-fat regimen. TLQP-21 exerted its effects by stimulating autonomic activation of adrenal medulla and adipose tissues.
Using microarray analysis, Hunsberger et al. (2007) found that exercise upregulated expression of Vgf in mouse hippocampus, a brain region implicated in mood and antidepressant responses. Administration of a synthetic Vgf-derived peptide produced an antidepressant response in mice, and, conversely, mutation of Vgf in mice produced the opposite effects.
Yamaguchi et al. (2007) found that Vgf mRNA was upregulated in the rat PVN and SON in response to water deprivation. They also found that Nerp1 and Nerp2 suppressed vasopressin release induced by intracerebroventricular injection of hypertonic NaCl or angiotensin II (106150) in rats. Nerps also suppressed basal and angiotensin II-induced vasopressin secretion from hypothalamic explants in vitro. Bioactivity of Nerps required C-terminal amidation. Anti-Nerp antibodies cancelled plasma vasopressin reduction in response to water loading, indicating that Nerps are potent endogenous suppressors of vasopressin release. Yamaguchi et al. (2007) concluded that NERPs modulate body fluid homeostasis.
Canu et al. (1997) demonstrated that the single-copy human VGF gene spans 6 kb of genomic DNA and contains 2 exons. The entire VGF protein is encoded by exon 2, while exon 1 contains only 5-prime untranslated sequence. The structural organization of the human gene is similar to that described for the rat VGF gene (Salton et al., 1991), and both the translated and the untranslated regions show a high degree of sequence homology to the rat gene.
By fluorescence in situ hybridization, Canu et al. (1997) assigned the VGF gene to 7q22.
Hahm et al. (1999) found that homozygous Vgf-null mice were small, hypermetabolic, hyperactive, and infertile. Vgf-null mice showed markedly reduced leptin (LEP; 164160) levels and fat stores and altered proopiomelanocortin (POMC; 176830), neuropeptide Y (NPY; 162640), and Agrp (602311) expression. Vgf mRNA was induced in hypothalamic arcuate nuclei of fasted normal mice. Hahm et al. (1999) suggested that VGF may have a role in regulation of energy homeostasis.
Bartolomucci, A., La Corte, G., Possenti, R., Locatelli, V., Rigamonti, A. E., Torsello, A., Bresciani, E., Bulgarelli, I., Rizzi, R., Pavone, F., D'Amato, F. R., Severini, C., and 13 others. TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity. Proc. Nat. Acad. Sci. 103: 14584-14589, 2006. [PubMed: 16983076] [Full Text: https://doi.org/10.1073/pnas.0606102103]
Canu, N., Possenti, R., Ricco, A. S., Rocchi, M., Levi, A. Cloning, structural organization analysis, and chromosomal assignment of the human gene for the neurosecretory protein VGF. Genomics 45: 443-446, 1997. [PubMed: 9344675] [Full Text: https://doi.org/10.1006/geno.1997.4945]
Ferri, G.-L., Possenti, R. vgf: a neurotrophin-inducible gene expressed in neuroendocrine tissues. Trends Endocr. Metab. 7: 233-239, 1996. [PubMed: 18406753] [Full Text: https://doi.org/10.1016/s1043-2760(96)00123-3]
Hahm, S., Mizuno, T. M., Wu, T. J., Wisor, J. P., Priest, C. A., Kozak, C. A., Boozer, C. N., Peng, B., McEvoy, R. C., Good, P., Kelley, K. A., Takahashi, J. S., Pintar, J. E., Roberts, J. L., Mobbs, C. V., Salton, R. J. Targeted deletion of the Vgf gene indicates that the encoded secretory peptide precursor plays a novel role in the regulation of energy balance. Neuron 23: 537-548, 1999. [PubMed: 10433265] [Full Text: https://doi.org/10.1016/s0896-6273(00)80806-5]
Hunsberger, J. G., Newton, S. S., Bennett, A. H., Duman, C. H., Russell, D. S., Salton, S. R., Duman, R. S. Antidepressant actions of the exercise-regulated gene VGF. Nature Med. 13: 1476-1482, 2007. [PubMed: 18059283] [Full Text: https://doi.org/10.1038/nm1669]
Levi, A., Eldridge, J. D., Paterson, B. M. Molecular cloning of a gene sequence regulated by nerve growth factor. Science 229: 393-395, 1985. [PubMed: 3839317] [Full Text: https://doi.org/10.1126/science.3839317]
Salton, S. R. J., Fischberg, D. J., Dong, K. W. Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells. Molec. Cell. Biol. 11: 2335-2349, 1991. [PubMed: 2017159] [Full Text: https://doi.org/10.1128/mcb.11.5.2335-2349.1991]
Yamaguchi, H., Sasaki, K., Satomi, Y., Shimbara, T., Kageyama, H., Mondal, M. S., Toshinai, K., Date, Y., Gonzalez, L. J., Shioda, S., Takao, T., Nakazato, M., Minamono, N. Peptidomic identification and biological validation of neuroendocrine regulatory peptide-1 and -2. J. Biol. Chem. 282: 26354-26360, 2007. [PubMed: 17609209] [Full Text: https://doi.org/10.1074/jbc.M701665200]