Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1990 Jan 1;110(1):1–12. doi: 10.1083/jcb.110.1.1

Sorting within the regulated secretory pathway occurs in the trans- Golgi network

PMCID: PMC2115992  PMID: 2295680

Abstract

Bioactive peptides cleaved from the egg-laying hormone precursor in the bag cell neurons of Aplysia are sorted into distinct dense core vesicle classes (DCVs). Bag cell prohormone processing can be divided into two stages, an initial cleavage occurring in a late Golgi compartment, which is not blocked by monensin, and later cleavages that occur within DCVs and are blocked by monensin. Prohormone intermediates are sorted in the trans-Golgi network. The large soma-specific DCVs turn over, while the small DCVs are transported to processes for regulated release. Thus, protein trafficking differentially regulates the levels and localization of multiple biologically active peptides derived from a common prohormone.

Full Text

The Full Text of this article is available as a PDF (3.7 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson R. G., Orci L. A view of acidic intracellular compartments. J Cell Biol. 1988 Mar;106(3):539–543. doi: 10.1083/jcb.106.3.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berry R. W., Arch S. Activation of neurosecretory cells enhances their synthesis of secretory protein. Brain Res. 1981 Jun 29;215(1-2):115–123. doi: 10.1016/0006-8993(81)90495-9. [DOI] [PubMed] [Google Scholar]
  3. Brown R. O., Mayeri E. Positive feedback by autoexcitatory neuropeptides in neuroendocrine bag cells of Aplysia. J Neurosci. 1989 Apr;9(4):1443–1451. doi: 10.1523/JNEUROSCI.09-04-01443.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burgess T. L., Kelly R. B. Constitutive and regulated secretion of proteins. Annu Rev Cell Biol. 1987;3:243–293. doi: 10.1146/annurev.cb.03.110187.001331. [DOI] [PubMed] [Google Scholar]
  5. CARO L. G., VAN TUBERGEN R. P., KOLB J. A. High-resolution autoradiography. I. Methods. J Cell Biol. 1962 Nov;15:173–188. doi: 10.1083/jcb.15.2.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Campbell C. H., Rome L. H. Coated vesicles from rat liver and calf brain contain lysosomal enzymes bound to mannose 6-phosphate receptors. J Biol Chem. 1983 Nov 10;258(21):13347–13352. [PubMed] [Google Scholar]
  7. Caro L. G. A common source of difficulty in high-resolution radioautography. J Cell Biol. 1969 Jun;41(3):918–919. doi: 10.1083/jcb.41.3.918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chiu A. Y., Strumwasser F. Two neuronal populations in the head ganglia of Aplysia californica with egg-laying hormone-like immunoreactivity. Brain Res. 1984 Feb 27;294(1):83–93. doi: 10.1016/0006-8993(84)91312-x. [DOI] [PubMed] [Google Scholar]
  9. Chung K. N., Walter P., Aponte G. W., Moore H. P. Molecular sorting in the secretory pathway. Science. 1989 Jan 13;243(4888):192–197. doi: 10.1126/science.2911732. [DOI] [PubMed] [Google Scholar]
  10. Crine P., Dufour L. Effects of monensin on the processing of pro-opiomelanocortin in the intermediate lobe of the rat pituitary. Biochem Biophys Res Commun. 1982 Nov 30;109(2):500–506. doi: 10.1016/0006-291x(82)91749-1. [DOI] [PubMed] [Google Scholar]
  11. Davidson H. W., Rhodes C. J., Hutton J. C. Intraorganellar calcium and pH control proinsulin cleavage in the pancreatic beta cell via two distinct site-specific endopeptidases. Nature. 1988 May 5;333(6168):93–96. doi: 10.1038/333093a0. [DOI] [PubMed] [Google Scholar]
  12. FRIEND D. S., MURRAY M. J. OSMIUM IMPREGNATION OF THE GOLGI APPARATUS. Am J Anat. 1965 Jul;117:135–149. doi: 10.1002/aja.1001170109. [DOI] [PubMed] [Google Scholar]
  13. Fisher J. M., Sossin W., Newcomb R., Scheller R. H. Multiple neuropeptides derived from a common precursor are differentially packaged and transported. Cell. 1988 Sep 9;54(6):813–822. doi: 10.1016/s0092-8674(88)91131-2. [DOI] [PubMed] [Google Scholar]
  14. Fumagalli G., Zanini A. In cow anterior pituitary, growth hormone and prolactin can be packed in separate granules of the same cell. J Cell Biol. 1985 Jun;100(6):2019–2024. doi: 10.1083/jcb.100.6.2019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gainer H., Sarne Y., Brownstein M. J. Neurophysin biosynthesis: conversion of a putative precursor during axonal transport. Science. 1977 Mar 25;195(4284):1354–1356. doi: 10.1126/science.65791. [DOI] [PubMed] [Google Scholar]
  16. Griffiths G., Hoflack B., Simons K., Mellman I., Kornfeld S. The mannose 6-phosphate receptor and the biogenesis of lysosomes. Cell. 1988 Feb 12;52(3):329–341. doi: 10.1016/s0092-8674(88)80026-6. [DOI] [PubMed] [Google Scholar]
  17. Griffiths G., Quinn P., Warren G. Dissection of the Golgi complex. I. Monensin inhibits the transport of viral membrane proteins from medial to trans Golgi cisternae in baby hamster kidney cells infected with Semliki Forest virus. J Cell Biol. 1983 Mar;96(3):835–850. doi: 10.1083/jcb.96.3.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Griffiths G., Simons K. The trans Golgi network: sorting at the exit site of the Golgi complex. Science. 1986 Oct 24;234(4775):438–443. doi: 10.1126/science.2945253. [DOI] [PubMed] [Google Scholar]
  19. Hand A. R., Oliver C. Relationship between the Golgi apparatus, GERL, and secretory granules in acinar cells of the rat exorbital lacrimal gland. J Cell Biol. 1977 Aug;74(2):399–413. doi: 10.1083/jcb.74.2.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hashimoto S., Fumagalli G., Zanini A., Meldolesi J. Sorting of three secretory proteins to distinct secretory granules in acidophilic cells of cow anterior pituitary. J Cell Biol. 1987 Oct;105(4):1579–1586. doi: 10.1083/jcb.105.4.1579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Johnson D. C., Schlesinger M. J. Vesicular stomatitis virus and sindbis virus glycoprotein transport to the cell surface is inhibited by ionophores. Virology. 1980 Jun;103(2):407–424. doi: 10.1016/0042-6822(80)90200-7. [DOI] [PubMed] [Google Scholar]
  22. Kauer J. A., Fisher T. E., Kaczmarek L. K. Alpha bag cell peptide directly modulates the excitability of the neurons that release it. J Neurosci. 1987 Nov;7(11):3623–3632. doi: 10.1523/JNEUROSCI.07-11-03623.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kelly R. B. Pathways of protein secretion in eukaryotes. Science. 1985 Oct 4;230(4721):25–32. doi: 10.1126/science.2994224. [DOI] [PubMed] [Google Scholar]
  24. Kreiner T., Sossin W., Scheller R. H. Localization of Aplysia neurosecretory peptides to multiple populations of dense core vesicles. J Cell Biol. 1986 Mar;102(3):769–782. doi: 10.1083/jcb.102.3.769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kupfermann I. Stimulation of egg laying: possible neuroendocrine function of bag cells of abdominal ganglion of Aplysia californica. Nature. 1967 Nov 25;216(5117):814–815. doi: 10.1038/216814a0. [DOI] [PubMed] [Google Scholar]
  26. Loh Y. P., Brownstein M. J., Gainer H. Proteolysis in neuropeptide processing and other neural functions. Annu Rev Neurosci. 1984;7:189–222. doi: 10.1146/annurev.ne.07.030184.001201. [DOI] [PubMed] [Google Scholar]
  27. Mayeri E., Rothman B. S., Brownell P. H., Branton W. D., Padgett L. Nonsynaptic characteristics of neurotransmission mediated by egg-laying hormone in the abdominal ganglion of Aplysia. J Neurosci. 1985 Aug;5(8):2060–2077. doi: 10.1523/JNEUROSCI.05-08-02060.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. McAllister L. B., Scheller R. H., Kandel E. R., Axel R. In situ hybridization to study the origin and fate of identified neurons. Science. 1983 Nov 18;222(4625):800–808. doi: 10.1126/science.6356362. [DOI] [PubMed] [Google Scholar]
  29. Newcomb R., Fisher J. M., Scheller R. H. Processing of the egg-laying hormone (ELH) precursor in the bag cell neurons of Aplysia. J Biol Chem. 1988 Sep 5;263(25):12514–12521. [PubMed] [Google Scholar]
  30. Newcomb R., Scheller R. H. Proteolytic processing of the Aplysia egg-laying hormone and R3-14 neuropeptide precursors. J Neurosci. 1987 Mar;7(3):854–863. doi: 10.1523/JNEUROSCI.07-03-00854.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Novikoff P. M., Novikoff A. B., Quintana N., Hauw J. J. Golgi apparatus, GERL, and lysosomes of neurons in rat dorsal root ganglia, studied by thick section and thin section cytochemistry. J Cell Biol. 1971 Sep;50(3):859–886. doi: 10.1083/jcb.50.3.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Orci L., Halban P., Amherdt M., Ravazzola M., Vassalli J. D., Perrelet A. A clathrin-coated, Golgi-related compartment of the insulin secreting cell accumulates proinsulin in the presence of monensin. Cell. 1984 Nov;39(1):39–47. doi: 10.1016/0092-8674(84)90189-2. [DOI] [PubMed] [Google Scholar]
  33. Orci L., Ravazzola M., Amherdt M., Perrelet A., Powell S. K., Quinn D. L., Moore H. P. The trans-most cisternae of the Golgi complex: a compartment for sorting of secretory and plasma membrane proteins. Cell. 1987 Dec 24;51(6):1039–1051. doi: 10.1016/0092-8674(87)90590-3. [DOI] [PubMed] [Google Scholar]
  34. Orci L., Ravazzola M., Storch M. J., Anderson R. G., Vassalli J. D., Perrelet A. Proteolytic maturation of insulin is a post-Golgi event which occurs in acidifying clathrin-coated secretory vesicles. Cell. 1987 Jun 19;49(6):865–868. doi: 10.1016/0092-8674(87)90624-6. [DOI] [PubMed] [Google Scholar]
  35. Pfeffer S. R., Rothman J. E. Biosynthetic protein transport and sorting by the endoplasmic reticulum and Golgi. Annu Rev Biochem. 1987;56:829–852. doi: 10.1146/annurev.bi.56.070187.004145. [DOI] [PubMed] [Google Scholar]
  36. Rothman B. S., Mayeri E., Brown R. O., Yuan P. M., Shively J. E. Primary structure and neuronal effects of alpha-bag cell peptide, a second candidate neurotransmitter encoded by a single gene in bag cell neurons of Aplysia. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5753–5757. doi: 10.1073/pnas.80.18.5753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rothman B. S., Weir G., Dudek F. E. Egg-laying hormone: direct action on the ovotestis of Aplysia. Gen Comp Endocrinol. 1983 Oct;52(1):134–141. doi: 10.1016/0016-6480(83)90166-1. [DOI] [PubMed] [Google Scholar]
  38. Salpeter M. M., Farquhar M. G. High resolution analysis of the secretory pathway in mammotrophs of the rat anterior pituitary. J Cell Biol. 1981 Oct;91(1):240–246. doi: 10.1083/jcb.91.1.240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Scheller R. H., Jackson J. F., McAllister L. B., Rothman B. S., Mayeri E., Axel R. A single gene encodes multiple neuropeptides mediating a stereotyped behavior. Cell. 1983 Jan;32(1):7–22. doi: 10.1016/0092-8674(83)90492-0. [DOI] [PubMed] [Google Scholar]
  40. Sossin W. S., Fisher J. M., Scheller R. H. Cellular and molecular biology of neuropeptide processing and packaging. Neuron. 1989 May;2(5):1407–1417. doi: 10.1016/0896-6273(89)90186-4. [DOI] [PubMed] [Google Scholar]
  41. Sossin W. S., Scheller R. H. A bag cell neuron-specific antigen localizes to a subset of dense core vesicles in Aplysia californica. Brain Res. 1989 Aug 14;494(2):205–214. doi: 10.1016/0006-8993(89)90588-x. [DOI] [PubMed] [Google Scholar]
  42. Tartakoff A. M. Perturbation of vesicular traffic with the carboxylic ionophore monensin. Cell. 1983 Apr;32(4):1026–1028. doi: 10.1016/0092-8674(83)90286-6. [DOI] [PubMed] [Google Scholar]
  43. Tooze J., Hollinshead M., Frank R., Burke B. An antibody specific for an endoproteolytic cleavage site provides evidence that pro-opiomelanocortin is packaged into secretory granules in AtT20 cells before its cleavage. J Cell Biol. 1987 Jul;105(1):155–162. doi: 10.1083/jcb.105.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Tooze J., Tooze S. A. Clathrin-coated vesicular transport of secretory proteins during the formation of ACTH-containing secretory granules in AtT20 cells. J Cell Biol. 1986 Sep;103(3):839–850. doi: 10.1083/jcb.103.3.839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Tooze J., Tooze S. A., Fuller S. D. Sorting of progeny coronavirus from condensed secretory proteins at the exit from the trans-Golgi network of AtT20 cells. J Cell Biol. 1987 Sep;105(3):1215–1226. doi: 10.1083/jcb.105.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Yates M. E., Berry R. W. Subcellular sites of processing of precursors to neurosecretory peptides in the bag cells of Aplysia: inferences from the effects of monensin, FCCP, and chloroquine. J Neurobiol. 1984 Mar;15(2):141–155. doi: 10.1002/neu.480150207. [DOI] [PubMed] [Google Scholar]
  47. von Figura K., Hasilik A. Lysosomal enzymes and their receptors. Annu Rev Biochem. 1986;55:167–193. doi: 10.1146/annurev.bi.55.070186.001123. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES