Mechanisms of Neuropeptide Precursor Processing

Implications for Neuropharmacology
  • Harold Gainer


In the past decade, more than 50 peptides have been identified in the nervous system as potential neurotransmitters and neuromodulators. These peptides produce distinct physiological and pharmacological effects on specific neurons, and are specifically localized and synthesized in the nervous system. Thus, in contrast to previous decades, when the neuropharmacologist needed to contend with only a few neurotransmitter candidates and receptor subtypes in the nervous system, the present situation abounds with an apparent “embarrassment of riches.” This diversity of potential intercellular peptidic messengers in the nervous system promises to become even more complex in the future for two reasons. First, new biologically active peptides will undoubtedly be discovered, and second, the biosynthetic mechanism for the generation of peptides is itself a potential generator of diversity. The generation of biologically active peptides involves the posttranslational processing of protein precursors (Douglass et al., 1984; Loh et al., 1984), which, in addition to containing the peptide sequence(s) of interest, also contain other (unpredictable) peptide sequences. Since the proteolytic cleavage processes are usually located in the secretory vesicles (Gainer et al., 1985), all these peptides will be cosecreted by exocytosis in response to a nerve impulse. While one of these secreted peptides may be the principal messenger at one site in the nervous system, any of the others could be the primary messenger at another site. In addition, variations in the posttranslational modifications of identical peptide precursors in different cells can lead to entirely different peptide products, with potentially different biological consequences (as for the case of proopiomelanocortin, see Chretien et al., this volume).


Secretory Vesicle Chromaffin Granule Magnocellular Neuron Neural Lobe Vasopressin Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Amico, J. A., and Robinson, A. G. (eds.), 1985, Oxytocin: Clinical and Laboratory Studies, Excerpta Medica, Amsterdam.Google Scholar
  2. Bargmann, W., and Scharrer, E., 1951, The origin of the posterior pituitary hormones, Am. Sci. 39:255–259.Google Scholar
  3. Bradbury, A. F., and Smyth, D. G., 1983a, Amidation of synthetic peptides by a pituitary enzyme: Specificity and mechanisms of the reaction, in: Peptides 1982 (K. Blaha and P. Mahlon, eds.), de Gruyter, Berlin, pp. 383–386.Google Scholar
  4. Bradbury, A. F., and Smyth, D. G., 1983b, Substrate specificity of an amidating enzyme in porcine pituitary, Biochem. Biophys. Res. Commun. 112:372–377.PubMedCrossRefGoogle Scholar
  5. Bradbury, A. F., Finnie, M. D. A., and Smyth, D. G., 1982, Mechanism of C-terminal amide formation by pituitary enzymes, Nature 298:686–688.PubMedCrossRefGoogle Scholar
  6. Brownstein, M. J., and Gainer, H., 1977, Neurophysin biosynthesis in normal rats and in rat with hereditary diabetes insipidus, Proc. Natl. Acad. Sci. USA 74:259–261.CrossRefGoogle Scholar
  7. Burbach, J. P., De Hoop, M. L., Schmale, H., Richter, D., De Kloet, E. R., Ten Haaf, J. A., and De Wied, D., 1984, Differential responses to osmotic stress of vasopressin-neurophysin mRNA in hypothalamic nuclei, Neuroendocrinology 39:582–584.PubMedCrossRefGoogle Scholar
  8. Casey, R. P., Njus, D., Radda, G. K., and Sehr, P. A., 1976, Adenosine triphosphate-evoked catecholamine release in chromaffin granules, osmotic lysis as a consequence of proton translocation, Biochem. J. 158:583–588.PubMedGoogle Scholar
  9. Casey, R. P., Njus, D., Radda, G. K., and Sehr, P. A., 1977, Active proton uptake by chromaffin granules: Observation by amine distribution and phosphorus-31 nuclear magnetic resonance techniques, Biochemistry 16:972–977.PubMedCrossRefGoogle Scholar
  10. Castel, M., Gainer, H., and Dellmann, H. D., 1984, Neuronal secretory systems, Int. Rev. Cytol. 88:303–459.PubMedCrossRefGoogle Scholar
  11. Clamagirand, C, Camier, M., Bousetta, H., Fahy, C, Morel, A., Nicholas, P., and Cohen, P., 1986, An endopeptidase associated with bovine neurohypophysis secretory granules cleaves pro-oxytocin/neurophysin peptide at paired basic residues, Biochem. Biophys. Res. Commun. 134:1190–1196.PubMedCrossRefGoogle Scholar
  12. Cross, B. A., and Leng, G. (eds.), 1983, The Neurohypophysis: Structure, Function and Control, Elsevier, Amsterdam.Google Scholar
  13. Dolais-Kitabgi, J., and Perlman, R. L., 1975, The stimulation of catecholamine release from chromaffin granules by valinomycin, Mol. Pharmacol. 11:745–750.PubMedGoogle Scholar
  14. Douglass, J., Civelli, O., and Herbert, E., 1984, Polyprotein gene expression: Generation of diversity of neuroendocrine peptides, Annu. Rev. Biochem. 53:665–715.PubMedCrossRefGoogle Scholar
  15. Drucker, D. J., Mojsov, S., and Habener, J. F., 1986, Cell-specific posttranslational processing of preproglucagon expressed from a metallothionein-glucagon fusion gene, J. Biol. Chem. 261:9637–9643.PubMedGoogle Scholar
  16. Duong, L., Fleming, P. J., and Russell, J. T., 1984, An identical cytochrome b561 is present in ovine adrenal chromaffin vesicles and posterior pituitary neurosecretory vesicles, J. Biol. Chem. 259:4885–4889.PubMedGoogle Scholar
  17. Eipper, B. A., Glembotski, C. C., and Mains, R. E., 1983a, Bovine intermediate pituitary α-amidation enzyme: Preliminary characterization, Peptides 4:921–928.PubMedCrossRefGoogle Scholar
  18. Eipper, B. A., Mains, R. E., and Glembotski, C. C., 1983b, Identification in pituitary tissue of a peptide α-amidation activity that acts on glycine-extended peptides and requires molecular oxygen, copper, and ascorbic acid, Proc. Natl. Acad. Sci. USA 80:5144–5148.PubMedCrossRefGoogle Scholar
  19. Eipper, B. A., Myers, A. C., and Mains, R. E., 1983c, Selective loss of α-melanotropin-amidating enzyme activity in primary cultures of rat intermediate pituitary cells, J. Biol. Chem. 258:7292–7298.PubMedGoogle Scholar
  20. Farquhar, M. G., and Palade, G. E., 1981, The Golgi apparatus (complex)—(1954–1981)—From artifact to center stage, J. Cell Biol. 91:77s–103s.PubMedCrossRefGoogle Scholar
  21. Flicker, L. D., and Snyder, S. H., 1982, Enkephalin convertase: Purification and characterization of a specific Encephalin-synthesizing carboxypeptidase localized to adrenal chromaffin granules, Proc. Natl. Acad. Sci. USA 79:3886–3890.CrossRefGoogle Scholar
  22. Flicker, L. D., and Snyder, S. H., 1983, Purification and characterization of enkephalin convertase, and enkephalin-synthesizing carboxypeptidase, J. Biol. Chem. 258:10950–10955.Google Scholar
  23. Fuller, P. J., Clements, J. A., Lolait, S. J., and Funder, J. W., 1984, Expression of the gene for arginine vasopressin in Brattleboro rats, J. Hyperten. 2:305–307.Google Scholar
  24. Fuller, P. J., Clements, J. A., and Funder, J. W., 1985, Localization of arginine-vasopressin-neurophysin II messenger ribonucleic acid in the hypothalamus of control and Brattleboro rats by hybridization histochemistry with a synthetic pentadecamer oligonucleotide probe, Endocrinology 116:2366–2388.CrossRefGoogle Scholar
  25. Gainer, H., Same, Y., and Brownstein, M. J., 1977a, Neurophysin biosynthesis: Conversion of a putative precursor during axonal transport, Science 195:1354–1356.PubMedCrossRefGoogle Scholar
  26. Gainer, H., Same, Y., and Brownstein, M. J., 1977b, Biosynthesis and axonal transport of rat neurohypophysial proteins and peptides, J. Cell Biol. 73:366–381.PubMedCrossRefGoogle Scholar
  27. Gainer, H., Russell, J. T., and Loh, Y. P., 1984, An aminopeptidase activity in bovine pituitary secretory vesicles that cleaves the N-terminal arginine from ß-lipotropin-60–65. FEBS Lett. 175:135–139.PubMedCrossRefGoogle Scholar
  28. Gainer, H., Russell, J. T., and Loh, Y. P., 1985, The enzymology and intracellular organization of peptide precursor processing: The secretory vesicle hypothesis, Neuroendocrinology 40:171–184.PubMedCrossRefGoogle Scholar
  29. Gillies, G., and Lowry, P., 1979, Corticotropin releasing factor may be modulated by vasopressin, Nature 278:463–464.PubMedCrossRefGoogle Scholar
  30. Glembotski, C. C., 1981, Subcellular fractionation studies on the posttranslational processing of pro-adrenocorticotropic hormone/endorphin in rat intermediate pituitary, J. Biol. Chem. 256:7433–7439.PubMedGoogle Scholar
  31. Glembotski, C. C., 1982, Characterization of the peptide acetyltransferase activity in bovine and rat intermediate pituitaries responsible for the acetylation of ß-endorphin and α-melanotropin, J. Biol. Chem. 257:10501–10509.PubMedGoogle Scholar
  32. Glembotski, C. C., Eipper, B. A., and Mains, R. E., 1984, Characterization of a peptide α-amidation activity from rat anterior pituitary, J. Biol. Chem. 259:6385–6392.PubMedGoogle Scholar
  33. Gordon-Weeks, R., Jones, P. M., and Robinson, I. E., 1983, Characterization of an intermediate in neurophysin biosynthesis in the guinea pig, FEBS Lett. 163:324–328.PubMedCrossRefGoogle Scholar
  34. Gubler, U., Seeburg, P., Hoffman, B. J., Gage, L. P., and Udenfriend, S., 1982, Molecular cloning establishes pro-enkephalin as precursor of encephalin-containing peptides, Nature 295:206–208.PubMedCrossRefGoogle Scholar
  35. Haddad, A., Guaraldo, S. P. M., Pelletier, G., Brasiliero, I. L. G., and Marchi, F., 1980, Glycoprotein secretion in the hypothalamoneurohypophysial system of the rat, Cell Tissue Res. 209:399–422.PubMedCrossRefGoogle Scholar
  36. Hampton, R. Y., and Holz, R. W., 1983, The effects of osmolality on the stability and function of cultured chromaffin cells and the role of osmotic forces in exocytosis, J. Cell Biol. 96:1082–1088.PubMedCrossRefGoogle Scholar
  37. Holz, R. W., 1986, The role of osmotic forces in exocytosis from adrenal chromaffin cells, Annu. Rev. Physiol. 48:175–189.PubMedCrossRefGoogle Scholar
  38. Ivell, R., and Richter, D., 1984, Structure and comparison of the oxytocin and vasopressin genes from rat, Proc. Natl. Acad. Sci. USA 81:2006–2010.PubMedCrossRefGoogle Scholar
  39. Johnson, R. G., and Scarpa, A., 1976, Ion permeability of isolated chromaffin vesicles, J. Gen. Physiol. 68:601–631.PubMedCrossRefGoogle Scholar
  40. Jones, M., Saermark, T., and Robinson, I. C., 1984, Conversion and release of an intermediate in vasopressin- neurophysin biosynthesis in the guinea pig, J. Endocrinol. 103:347–354.PubMedCrossRefGoogle Scholar
  41. Kakidani, H., Furutani, Y., Takahashi, H., Noda, M., Morimoto, Y., Hirose, T., Asai, M., Inayama, S., Nakanashi, S., and Numa, S., 1982, Cloning and sequence analysis of cDNA for porcine ß-en-dorphin/dynorphin precursor, Nature 298:245–249.PubMedCrossRefGoogle Scholar
  42. Kemmler, W., Steiner, D. F., and Borg, J., 1973, Studies on the conversion of proinsulin to insulin, J. Biol. Chem. 248:4544–4551.PubMedGoogle Scholar
  43. Kent, C, and Williams, M. A., 1974, The nature of the hypothalamo-neurohypophysial neurosecretion in rat: A study by light- and electron microscope autoradiography, J. Cell Biol. 60:554–570.PubMedCrossRefGoogle Scholar
  44. Knight, D. E., 1986, Calcium and exocytosis, Ciba Found. Symp. 122:250–269.PubMedGoogle Scholar
  45. Knight, D. E., and Baker, P. F., 1982, Calcium-dependence of catecholamine release from bovine adrenal medullary cells after exposure to intense electric fields, Membr. Biol. 68:107–140.CrossRefGoogle Scholar
  46. Koch, G., and Richter, D. (eds.), 1980, Biosynthesis, Modification, and Processing of Cellular and Viral Polyproteins, Academic Press, New York.Google Scholar
  47. Krieger-Brauer, H., and Gratzl, M., 1983, Effects of monovalent and divalent cations on Ca+ + fluxes across chromaffin secretory membrane vesicles, J. Neurochem. 41:1269–1276.PubMedCrossRefGoogle Scholar
  48. Land, H., Schutz, G., Schmale, H., and Richter, D., 1982, Nucleotide sequence of cloned cDNA encoding bovine arginine vasopressin-neurophysin II precursor, Nature 295:299–303.PubMedCrossRefGoogle Scholar
  49. Land, H., Grez, M., Ruppert, S., Schmale, H., Rehbein, M., Richter, D., and Schutz, G., 1983, Deduced amino acid sequence from the bovine oxytocin-neurophysin 1 precursor cDNA, Nature 302:342–344.PubMedCrossRefGoogle Scholar
  50. Loh, Y. P., 1986, Kinetic studies on the processing of ßh–lipoprotein by bovine pituitary intermediate lobe pro-opiomelanocortin converting enzyme, J. Biol. Chem. 261:11949–11952.PubMedGoogle Scholar
  51. Loh, Y. P., Brownstein, M. J., and Gainer, H., 1984, Proteolysis in neuropeptide processing and other neural functions, Annu. Rev. Neurosci. 7:189–222.PubMedCrossRefGoogle Scholar
  52. Loh, Y. P., Parish, D. C., and Tuteja, R., 1985, Purification and characterization of a paired basic residue-specific pro-opiomelanocortin converting enzyme from bovine pituitary intermediate lobe secretory vesicles, J. Biol. Chem. 260:7194–7205.PubMedGoogle Scholar
  53. Majzoub, J. A., 1985, Vasopressin biosynthesis, in: Vasopressin (R. W. Schrier, ed.), Raven Press, New York, pp. 465–474.Google Scholar
  54. Majzoub, J. A., Rich, A., Van Boom, J., and Habener, J., 1983, Vasopressin and oxytocin mRNA regulation in the rat assessed by hybridization with synthetic oligonucleotides, J. Biol. Chem. 258:14061–14064.PubMedGoogle Scholar
  55. Majzoub, J. A., Pappey, A., Burg, R., and Habener, J., 1984, Vasopressin gene is expressed at low levels in the hypothalamus of the Brattleboro rat, Proc. Natl. Acad. Sci. USA 81:5296–5299.PubMedCrossRefGoogle Scholar
  56. Moore, H. P., Gumbiner, B., and Kelley, R. B., 1983a, Chloroquine diverts ACTH from a regulated to a constitutive pathway in AtT-20 cells, Nature 302:434–436.PubMedCrossRefGoogle Scholar
  57. Moore, H. P., Walker, M., Lee, F., and Kelley, R. B., 1983b, Expressing a human proinsulin cDNA in a mouse ACTH secreting cell: Intracellular storage, processing, and secretion on stimulation, Cell 35:531–538.PubMedCrossRefGoogle Scholar
  58. Morris, J. F., Nordmann, J. J., and Dyball, R. E. J., 1978, Structure-function correlation in mammalian neurosecretion, Int. Rev. Exp. Pathol. 18:1–95.PubMedGoogle Scholar
  59. Murthy, A. S. N., Mains, R. E., and Eipper, B. A., 1986, Purification and characterization of peptidylglycine- α -amidating monooxygenase from bovine neurointermediate pituitary, J. Biol. Chem. 261:1815–1822.PubMedGoogle Scholar
  60. Nakanishi, S., Inoue, A., Kita, T., Nakamura, M., Chang, A. C. Y., Cohen, S. N., and Numa, S., 1979, Nucleotide sequence of cloned cDNA for bovine corticotropin-ß-lipotropin precursor, Nature 278:423–427.PubMedCrossRefGoogle Scholar
  61. Noda, M., Teranishi, Y., Takahashi, H., Toyosato, M., Notake, M., Nakanishi, S., and Numa, S., 1982, Isolation and structural organization of the human preproenkephalin gene, Nature 297:432–434.CrossRefGoogle Scholar
  62. Nojiri, H., Sato, M., and Urano, A., 1985, In situ hybridization of the vasopressin mRNA in the rat hypothalamus by use of a synthetic oligonucleotide probe, Neurosci. Lett. 58:101–105.PubMedCrossRefGoogle Scholar
  63. Nordmann, J. J., and Morris, J. F., 1982, Neurosecretory granules, in: Neurotransmitter Vesicles (R. L. Klein, H. Lagercrantz, and H. Zimmerman, eds.), Academic Press, New York, pp. 41–64.Google Scholar
  64. North, W. G., Mitchell, T., and North, G. M., 1983, Characteristics of a precursor to vasopressin-associated bovine neurophysin, FEBS Lett. 152:29–34.PubMedCrossRefGoogle Scholar
  65. Parish, D. C., Tutega, R., Altstein, M., Gainer, H., and Loh, Y. P., 1986, Purification and characterization of a paired-basic residue specific prohormone converting enzyme from bovine pituitary neural lobe secretory vesicles, J. Biol. Chem. 261:14392–14397.PubMedGoogle Scholar
  66. Pazzoles, C. J., and Pollard, H. B., 1978, Evidence for stimulation of anion transport in ATP-evoked transmitter release from isolated secretory vesicles, J. Biol. Chem. 253:3962–3969.Google Scholar
  67. Pazzoles, C. J., Creutz, C. E., Ramu, A., and Pollard, H. B., 1980, Permeant anion activation of MgATPase activity in chromaffin granules, J. Biol. Chem. 255:7863–7869.Google Scholar
  68. Phillips, J. H., 1977, Passive ion permeability of the chromaffin granule membrane, Biochem. J. 186:289–297.Google Scholar
  69. Picaud, S., Marty, A., Trautmann, O. G.-W., and Henry, J.-P., 1984, Incorporation of chromaffin granule membranes into large-size vesicles suitable for patch-clamp recording, FEBS Lett. 178:20–24.PubMedCrossRefGoogle Scholar
  70. Pollard, H. B., Pazoles, C. J., and Creutz, C. E., 1981, Mechanism of calcium action and release of vesicle-bound hormones during exocytosis, Recent Prog. Horm. Res. 37:299–332.PubMedGoogle Scholar
  71. Robinson, I. C., and Jones, P. M., 1983, An intermediate in the biosynthesis of vasopressin and neurophysin in the guinea pig posterior pituitary, Neurosci. Lett. 39:273–278.PubMedCrossRefGoogle Scholar
  72. Ruppert, S. D., Scherer, G., and Schutz, G., 1984, Recent gene conversion involving bovine vasopressin and oxytocin precursor genes suggested by nucleotide sequence, Nature 308:554–557.PubMedCrossRefGoogle Scholar
  73. Russell, J. T., 1981, Isolation of purified neurosecretory vesicles from bovine neurohypophyses using isoosmolar density gradients, Anal. Biochem. 113:229–238.PubMedCrossRefGoogle Scholar
  74. Russell, J. T., 1984, ΔpH, H+ diffusion potentials, and Mg+ + ATPase in neurosecretory vesicles isolated from bovine neurohypophyses, J. Biol. Chem. 259:9496–9507.PubMedGoogle Scholar
  75. Russell, J. T., and Holz, R., 1981, Measurement of ΔpH and membrane potential in isolated neurosecretory vesicles from bovine neurohypophyses, J. Biol. Chem. 256:5950–5953.PubMedGoogle Scholar
  76. Sachs, H., Fawcett, P., Takabatake, Y., and Portanova, R., 1969, Biosynthesis and release of vasopressin and neurophysin, Recent Prog. Horm. Res. 25:447–491.PubMedGoogle Scholar
  77. Sausville, E., Carney, D., and Battey, J., 1985, The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line, J. Biol. Chem. 260:10236–10241.PubMedGoogle Scholar
  78. Schmale, H., and Richter, D., 1984, Single base deletion in the vasopressin gene is the cause of diabetes insipidus in Brattleboro rats, Nature 308:705–709.PubMedCrossRefGoogle Scholar
  79. Schmale, H., Heinsohn, S., and Richter, D., 1983, Structural organization of the rat gene for the arginine-Vasopressin-neurophysin precursor, EMBO J. 2:763–767.PubMedGoogle Scholar
  80. Schmale, H., Ivell, R., Breindel, M., Darmer, D., and Richter, D., 1984, The mutant vasopressin gene from diabetes insipidus (Brattleboro) rats is transcribed but the message is not efficiently translated, EMBO J. 3:3289–3293.PubMedGoogle Scholar
  81. Schrier, R. W. (ed.), 1985, Vasopressin, Raven Press, New York.Google Scholar
  82. Sherman, T. G., Akil, H., and Watson, S. J., 1985, Vasopressin mRNA expression: A Northern and in situ hybridization analysis, in: Vasopressin (R.W. Schrier, ed.), Raven Press, New York, pp. 475–484.Google Scholar
  83. Silverman, A., and Zimmerman, E. A., 1983, Magnocellular neurosecretory system, Annu. Rev. Neurosci. 6:357–380.PubMedCrossRefGoogle Scholar
  84. Sofroniew, M. V., 1985, Vasopressin, oxytocin and their related neurophysins, in: Handbook of Chemical Neuroanatomy, Vol. 4, Part I (A. Bjorklund and T. Hökfelt, eds.), Elsevier, Amsterdam, pp. 93–165.Google Scholar
  85. Stanley, E. F., and Ehrenstein, G., 1985, A model for exocytosis based on the opening of calcium-activated potassium channels in vesicles, Life Sci. 37:1985–1995.PubMedCrossRefGoogle Scholar
  86. Stanley, E. F., Ehrenstein, G., and Russell, J. T., 1986a, Evidence for calcium-activated potassium channels in vesicles of pituitary cells, Biophys. J. 49:19a.CrossRefGoogle Scholar
  87. Steiner, D. F., Kemmier, W., Tager, H. S., and Peterson, J. D., 1974, Proteolytic processing in the biosynthesis of insulin and other proteins, Fed. Proc. 33:2105–2115.PubMedGoogle Scholar
  88. Swanson, L. W., and Sawchenko, P. E., 1983, Hypothalamic integration: Organization of the paraventricular and supraoptic nuclei, Annu. Rev. Neurosci. 6:269–324.PubMedCrossRefGoogle Scholar
  89. Uhl, G. R., and Reppert, S. M., 1986, Suprachiasmatic nucleus vasopressin messenger RNA: Circadian variation in normal and Brattleboro rats, Science 232:390–393.PubMedCrossRefGoogle Scholar
  90. Uhl, G. R., Zingg, H. H., and Habener, J. F., 1985, Vasopressin mRNA in situ hybridization: Localization and regulation studied with oligonucleotide cDNA probes in normal and Brattleboro rat hypothalamus, Proc. Natl. Acad. Sci. USA 82:5555–5559.PubMedCrossRefGoogle Scholar
  91. Valtin, H., Stewart, J., and Sokol, H. W., 1974, Genetic control of the production of posterior pituitary principles, in: Handbook of Physiology, Section 7, Vol. IV, Part I (R. O. Gree and E. B. Astwood, eds.), American Physiological Society, Washington, D.C., pp. 131–171.Google Scholar
  92. Whitnall, M. H., Gainer, H., Cox, B. M., and Molineaux, C. J., 1983, Dynorphin-A-(l–8) is contained within vasopressin neurosecretory vesicles in rat pituitary, Science 222:1137–1139.PubMedCrossRefGoogle Scholar
  93. Whitnall, M. H., Mezey, E., and Gainer, H., 1985, Co-localization of corticotropin releasing factor and vasopressin in median eminence neurosecretory vesicles, Nature 317:248–250.PubMedCrossRefGoogle Scholar
  94. Wolfson, B., Manning, R. W., Davis, L. G., Arentzen, R., and Baldino, F., Jr., 1985, Co-localization of corticotropin releasing factor and vasopressin mRNA in neurons after adrenalectomy, Nature 315:59–61.PubMedCrossRefGoogle Scholar
  95. Zimmerman, M., Mumford, R. A., and Steiner, D. F., 1980, Precursor processing in the biosynthesis of proteins, Ann. N.Y. Acad. Sci. 343:1–449.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Harold Gainer
    • 1
  1. 1.Laboratory of Neurochemistry and Neuroimmunology, National Institute of Child Health and Human Development, National Institutes of HealthBethesdaUSA

Personalised recommendations