Nature 323, 82 - 86 (04 September 1986); doi:10.1038/323082a0

Bovine chromogranin A sequence and distribution of its messenger RNA in endocrine tissues

Anna Iacangelo^*, Hans-Urs Affolter^*, Lee E. Eiden^*‡, Edward Herbert^† & Mark Grimes^†

^*Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, Maryland 20892, USA
^†Institute for Advanced Biomedical Research, The Oregon Health Sciences University, Portland, Oregon 97201, USA
^‡To whom correspondence should be addressed

Chromogranin A is contained in storage vesicles of chromaffin cells of the adrenal medulla and released with catecholamines when the splanchnic nerve is stimulated^1,2. Chromogranin A is similar to secretory protein I (SP-I), a major secreted protein of the parathyroid³. Chromogranin A/SP-I immunoreactivity is abundant in endocrine cells that secrete peptide hormones from storage vesicles⁴⁻⁷. Chromogranins may act in neuroendocrine secretion by binding intravesicular calcium^8,9. Serum levels of chromogranin are raised in hypertension¹⁰ and endocrine neoplasia^8,10,11. We report here the isolation and sequencing of a cDNA encoding bovine chromogranin A, providing the first complete primary structure of a chromogranin protein. Chromogranin A is a highly acidic protein with an apparent relative molecular mass (M _r) of 75,000 on SDS-PAGE, but an actual M _r of 48,000. Adrenal medulla, brain, pituitary and parathyroid are all sites of synthesis of chromogranin A. The primary structure of chromogranin A, and the presence of chromogranin mRNA in the parathyroid, indicate that chromogranin A and SP-I are identical.

References

1.	Blashko, H., Comline, R. S., Schneider, F. H., Silver, M. & Smith, A. D. Nature 215, 58−59 (1967). | PubMed | ISI | ChemPort |
2.	Winkler, H. Neuroscience 1, 65−80 (1976). | Article | PubMed | ISI | ChemPort |
3.	Cohn, D. V. et al. Proc. natn. Acad. Sci. U.S.A. 79, 6056−6059 (1982). | ChemPort |
4.	Cohn, D. V., Elting, J. J., Frick, M. & Elde, R. Endocrinology 114, 1963−1974 (1984). | PubMed | ISI | ChemPort |
5.	O'Connor, D. T., Burton, D. & Deftos, L. J. Life Sci. 33, 1657−1663 (1983). | Article | PubMed | ChemPort |
6.	Somogyi, P. et al. Brain Res. Rev. 8 193−230 (1984). | Article | ISI | ChemPort |
7.	Angeletti, R. H. & Hickey, W. F. Science 230, 89−90 (1985). | PubMed | ISI | ChemPort |
8.	O'Connor, D. T., Parmer, R. J. & Deftos, L. J. Trans. Ass. Am. Physicians 97, 242−250 (1984). | ChemPort |
9.	Reiffen, F. U. & Gratzl, M. FEBS Letts. 195, 327−330 (1986). | Article | ChemPort |
10.	O'Connor, D. T. & Bernstein, K. N. New Engl. J. Med. 311, 764−770 (1984). | PubMed | ChemPort |
11.	Wilson, B. S. & Lloyd, R. V. Am. J. Pathol. 115, 458−468 (1984). | PubMed | ISI | ChemPort |
12.	Kiang, W. L., Krusius, T., Finne, J., Margolis, R. U. & Margolis, R. K. J. biol. Chem. 257, 1651−1657 (1982). | PubMed | ISI | ChemPort |
13.	Kruggel, W., O'Connor, D. T. & Lewis, R. V. Biochem. biophys. Res. Commun. 127, 380−383 (1985). | PubMed | ISI | ChemPort |
14.	Hogue Angeletti, R. Arch. Biochem. Biophys. 184, 364−372 (1977). | PubMed | ChemPort |
15.	Settleman, J., Nolan, J. & Hogue Angeletti, R. J. biol. Chem. 260, 1641−1644 (1985). | PubMed | ISI | ChemPort |
16.	Hutton, J. C., Hansen, F. & Peshavaria, M. FEBS Lett. 188, 336−340 (1985). | Article | PubMed | ISI | ChemPort |
17.	Settleman, J., Fonseca, R., Nolan, J. & Hogue Angeletti, R. J. biol Chem. 260, 1645−1651 (1985). | PubMed | ISI | ChemPort |
18.	Majzoub, J. A., Kronenberg, H. M., Potts, J. T. Jr, Rich, A. & Habener, J. F. J. biol Chem. 254, 7449−7455 (1979). | PubMed | ISI | ChemPort |
19.	Hamilton, J. W., Chu, L. L. H., Rouse, J. B., Reddig, K. & MacGregor, R. R. Arch. Biochem. Biophys. 244, 16−26 (1986). | PubMed | ISI | ChemPort |
20.	Poisner, A. M. & Trifaro, J. M. (eds) The Secretory Granule (Elsevier, Amsterdam, 1982).
21.	Ostwald, T. J., MacLennan, D. H. & Dorrington, K. J. J. biol. Chem. 249, 5867−5871 (1974). | PubMed | ISI | ChemPort |
22.	Wasserman, R. H., Corradino, R. A. & Taylor, A. N. J. biol. Chem. 243, 3978−3986 (1968). | PubMed | ISI | ChemPort |
23.	Isobe, T. & Okuyama, T. Eur. J. Biochem. 89, 379−388 (1978). | PubMed | ISI | ChemPort |
24.	Kligman, D. & Marshak, D. R. Proc. natn. Acad. Sci U.S.A. 82, 7136−7139 (1985). | ChemPort |
25.	Davies, R. W. in Gel Electrophoresis of Nucleic Acids, A Practical Approach (eds Rickwood, D. & Hames, B. D.) 117−172 (IRL, Oxford, 1982).
26.	Maniatis, T., Fritsch, E. F. & Sambrook, J. Molecular Cloning, A Laboratory Manual (Cold Spring Harbor Laboratory, New York, 1982).
27.	Okayama, H. & Berg, P. Molec. Cell Biol. 3, 280−289 (1983). | PubMed | ISI | ChemPort |
28.	Hanahan, D. in DNA Cloning, A Practical Approach Vol. 1 (ed. Glover, D. M.) 109−135 (IRL, Oxford, 1985).
29.	Gubler, U., Seeburg, P. H., Hoffman, B. J., Gage, L. P. & Udenfriend, S. Nature 295, 206−208 (1982). | PubMed | ISI | ChemPort |
30.	Ehrhart, M. et al. J. Histochem. Cytochem. 34 (in the press). | PubMed |
31.	Benedum, B. et al. EMBO J. 5, 1495 (1986). | PubMed | ISI |