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. 1984 Dec 20;3(13):3183–3189. doi: 10.1002/j.1460-2075.1984.tb02277.x

Relationship between levels of nerve growth factor (NGF) and its messenger RNA in sympathetic ganglia and peripheral target tissues.

R Heumann, S Korsching, J Scott, H Thoenen
PMCID: PMC557836  PMID: 6549295

Abstract

We have developed a sensitive assay for the quantification of nerve growth factor mRNA (mRNANGF) in various tissues of the mouse using in vitro transcribed RNANGF. Probes of both polarities were used to determine the specificity of the hybridization signals obtained. Comparison of NGF levels with its mRNA revealed that both were correlated with the density of sympathetic innervation. Thus, vas deferens contained high levels of both NGF and mRNANGF, whereas skeletal muscle levels were barely detectable, indicating that in peripheral tissues NGF levels are primarily regulated by the quantity of mRNANGF and not by the rate of processing of NGF precursor to NGF. However, although superior cervical ganglia contained the highest levels of NGF, its mRNA was barely detectable. Thus, the high levels of NGF in sympathetic ganglia result from retrograde axonal transport rather than local synthesis. The quantity of NGF found in the submandibular glands of female animals was three orders of magnitude higher than expected from their mRNA levels. This observation is discussed in the context of the difference between the mechanism of storage and exocytosis of exocrine glands versus the constitutive release from other tissues.

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Selected References

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  1. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barde Y. A., Edgar D., Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1982;1(5):549–553. doi: 10.1002/j.1460-2075.1982.tb01207.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barth E. M., Korsching S., Thoenen H. Regulation of nerve growth factor synthesis and release in organ cultures of rat iris. J Cell Biol. 1984 Sep;99(3):839–843. doi: 10.1083/jcb.99.3.839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chan Y. L., Olvera J., Wool I. G. The structure of rat 28S ribosomal ribonucleic acid inferred from the sequence of nucleotides in a gene. Nucleic Acids Res. 1983 Nov 25;11(22):7819–7831. doi: 10.1093/nar/11.22.7819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cohen S. PURIFICATION OF A NERVE-GROWTH PROMOTING PROTEIN FROM THE MOUSE SALIVARY GLAND AND ITS NEURO-CYTOTOXIC ANTISERUM. Proc Natl Acad Sci U S A. 1960 Mar;46(3):302–311. doi: 10.1073/pnas.46.3.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Darling T. L., Petrides P. E., Beguin P., Frey P., Shooter E. M., Selby M., Rutter W. J. The biosynthesis and processing of proteins in the mouse 7S nerve growth factor complex. Cold Spring Harb Symp Quant Biol. 1983;48(Pt 1):427–434. doi: 10.1101/sqb.1983.048.01.047. [DOI] [PubMed] [Google Scholar]
  7. Gumbiner B., Kelly R. B. Two distinct intracellular pathways transport secretory and membrane glycoproteins to the surface of pituitary tumor cells. Cell. 1982 Jan;28(1):51–59. doi: 10.1016/0092-8674(82)90374-9. [DOI] [PubMed] [Google Scholar]
  8. Hahn W. E., Chaudhari N., Beck L., Wilber K., Peffley D. Genetic expression and postnatal development of the brain: some characteristics of nonpolyadenylated mRNAs. Cold Spring Harb Symp Quant Biol. 1983;48(Pt 2):465–475. doi: 10.1101/sqb.1983.048.01.051. [DOI] [PubMed] [Google Scholar]
  9. Harper G. P., Glanville R. W., Thoenen H. The purification of nerve growth factor from bovine seminal plasma. Biochemical characterization and partial amino acid sequence. J Biol Chem. 1982 Jul 25;257(14):8541–8548. [PubMed] [Google Scholar]
  10. Herbert E., Oates E., Martens G., Comb M., Rosen H., Uhler M. Generation of diversity and evolution of opioid peptides. Cold Spring Harb Symp Quant Biol. 1983;48(Pt 1):375–384. doi: 10.1101/sqb.1983.048.01.041. [DOI] [PubMed] [Google Scholar]
  11. Hirata Y., Orth D. N. Secretion of epidermal growth factor, nerve growth factor, and renin-like enzymes by dispersed male mouse submandibular gland cells in vitro. Endocrinology. 1980 Jul;107(1):92–97. doi: 10.1210/endo-107-1-92. [DOI] [PubMed] [Google Scholar]
  12. Korsching S., Thoenen H. Nerve growth factor in sympathetic ganglia and corresponding target organs of the rat: correlation with density of sympathetic innervation. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3513–3516. doi: 10.1073/pnas.80.11.3513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Melera P. W., Rusch H. P. A characterization of ribonucleic acid in the myxomycete Physarum polycephalum. Exp Cell Res. 1973 Nov;82(1):197–209. doi: 10.1016/0014-4827(73)90262-0. [DOI] [PubMed] [Google Scholar]
  14. Ouellette A. J. Purification by benzoylated cellulose chromatography of translatable messenger ribonucleic acid lacking polyadenylate. J Biol Chem. 1980 Apr 10;255(7):2740–2746. [PubMed] [Google Scholar]
  15. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  16. Schwab M. E., Stöckel K., Thoenen H. Immunocytochemical localization of nerve growth factor (NGF) in the submandibular gland of adult mice by light and electron microscopy. Cell Tissue Res. 1976 Jun 28;169(3):289–299. doi: 10.1007/BF00219602. [DOI] [PubMed] [Google Scholar]
  17. Scott J., Selby M., Urdea M., Quiroga M., Bell G. I., Rutter W. J. Isolation and nucleotide sequence of a cDNA encoding the precursor of mouse nerve growth factor. Nature. 1983 Apr 7;302(5908):538–540. doi: 10.1038/302538a0. [DOI] [PubMed] [Google Scholar]
  18. Tartakoff A., Vassalli P., Détraz M. Comparative studies of intracellular transport of secretory proteins. J Cell Biol. 1978 Dec;79(3):694–707. doi: 10.1083/jcb.79.3.694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Thoenen H., Barde Y. A. Physiology of nerve growth factor. Physiol Rev. 1980 Oct;60(4):1284–1335. doi: 10.1152/physrev.1980.60.4.1284. [DOI] [PubMed] [Google Scholar]
  20. Thoenen H., Korsching S., Barde Y. A., Edgar D. Quantitation and purification of neurotrophic molecules. Cold Spring Harb Symp Quant Biol. 1983;48(Pt 2):679–684. doi: 10.1101/sqb.1983.048.01.071. [DOI] [PubMed] [Google Scholar]
  21. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tullis R. H., Rubin H. Calcium protects DNase I from proteinase K: a new method for the removal of contaminating RNase from DNase I. Anal Biochem. 1980 Sep 1;107(1):260–264. doi: 10.1016/0003-2697(80)90519-9. [DOI] [PubMed] [Google Scholar]
  23. Ullrich A., Gray A., Berman C., Dull T. J. Human beta-nerve growth factor gene sequence highly homologous to that of mouse. Nature. 1983 Jun 30;303(5920):821–825. doi: 10.1038/303821a0. [DOI] [PubMed] [Google Scholar]

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