Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1970 Dec 1;47(3):745–766. doi: 10.1083/jcb.47.3.745

GROWTH AND DIFFERENTIATION OF CYTOPLASMIC MEMBRANES IN THE COURSE OF LIPOPROTEIN GRANULE SYNTHESIS IN THE HEPATIC CELL

I. Elaboration of Elements of the Golgi Complex

Albert Claude 1
PMCID: PMC2108163  PMID: 5497550

Abstract

The synthesis of "very low" density lipoprotein in liver cells is characterized by the fact that the synthesized products, mostly triglycerides, are processed in the form of discrete, size-limited granules or globules, about 400 A in diameter. The present investigation has been made possible in part by the use of a fixative (OsO4 in bidistilled H2O at pH 6.0, in the absence of electrolytes) particularly effective in preserving cytoplasmic membranes and lipids, and giving them high stainability and differential contrast. Under these technical conditions, the lipoprotein granules retain their morphology and high density to electrons practically unaltered, and may serve as tracers in determining their route of transport from the sites of synthesis, starting at the rough-smooth ER junctions, to the lumen of Golgi concentrating vesicles. From the observations, it may be deduced that, along with lipoprotein granule synthesis and transport, there are also production and transfer of new membranes in the form of tubular extensions of smooth ER network which, by progressive fusion and coalescence, participate in the elaboration of fenestrated plates and solid Golgi sacs. In contradistinction to the entire process of liver lipoprotein granule synthesis, transport, and segregation, as reported in the present paper, appears to constitute a developmental sequence which includes the following communicating compartments, in consecutive order: cisternae of rough ER where proteins and possibly phospholipids are synthesized, smooth ER network where triglycerides are synthesized and transported in the form of dense granules, fusion of smooth ER tubular extensions into Golgi fenestrated plates, and further coalescence into solid Golgi sacs, ending in the segregation of the granules in appended concentrating vesicles, or detached "secretory vesicles." It seems that it is this progressive evolution in growth and configuration of membranes which is reflected in the so called polarity, from forming to mature faces, of the Golgi apparatus.

Full Text

The Full Text of this article is available as a PDF (2.8 MB).

Selected References

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

  1. Baglio C. M., Farber E. Reversal by adenine of the ethionine-induced lipid accumulation in the endoplasmic reticulum of the rat liver. A preliminary report. J Cell Biol. 1965 Dec;27(3):591–601. doi: 10.1083/jcb.27.3.591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bainton D. F., Farquhar M. G. Differences in enzyme content of azurophil and specific granules of polymorphonuclear leukocytes. II. Cytochemistry and electron microscopy of bone marrow cells. J Cell Biol. 1968 Nov;39(2):299–317. doi: 10.1083/jcb.39.2.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bainton D. F., Farquhar M. G. Origin of granules in polymorphonuclear leukocytes. Two types derived from opposite faces of the Golgi complex in developing granulocytes. J Cell Biol. 1966 Feb;28(2):277–301. doi: 10.1083/jcb.28.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beams H. W., Kessel R. G. The Golgi apparatus: structure and function. Int Rev Cytol. 1968;23:209–276. doi: 10.1016/s0074-7696(08)60273-9. [DOI] [PubMed] [Google Scholar]
  5. CARO L. G., PALADE G. E. PROTEIN SYNTHESIS, STORAGE, AND DISCHARGE IN THE PANCREATIC EXOCRINE CELL. AN AUTORADIOGRAPHIC STUDY. J Cell Biol. 1964 Mar;20:473–495. doi: 10.1083/jcb.20.3.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CLAUDE A. Problems of fixation for electron microscopy. Results of fixation with osmium tetroxide in acid and alkaline media. Pathol Biol. 1961 Apr;9:933–947. [PubMed] [Google Scholar]
  7. Cunningham W. P., Morré D. J., Mollenhauer H. H. Structure of isolated plant Golgi apparatus revealed by negative staining. J Cell Biol. 1966 Feb;28(2):169–179. doi: 10.1083/jcb.28.2.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DALTON A. J., FELIX M. D. A comparative study of the Golgi complex. J Biophys Biochem Cytol. 1956 Jul 25;2(4 Suppl):79–84. doi: 10.1083/jcb.2.4.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DALTON A. J., FELIX M. D. Cytologic and cytochemical characteristics of the Golgi substance of epithelial cells of the epididymis in situ, in homogenates and after isolation. Am J Anat. 1954 Mar;94(2):171–207. doi: 10.1002/aja.1000940202. [DOI] [PubMed] [Google Scholar]
  10. Fleischer B., Fleischer S., Ozawa H. Isolation and characterization of Golgi membranes from bovine liver. J Cell Biol. 1969 Oct;43(1):59–79. doi: 10.1083/jcb.43.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Flickinger C. J. Fenestrated cisternae in the Golgi apparatus of the epididymis. Anat Rec. 1969 Jan;163(1):39–53. doi: 10.1002/ar.1091630105. [DOI] [PubMed] [Google Scholar]
  12. Flickinger C. J. The pattern of growth of the Golgi complex during the fetal and postnatal development of the rat epididymis. J Ultrastruct Res. 1969 May;27(3):344–360. doi: 10.1016/s0022-5320(69)80022-5. [DOI] [PubMed] [Google Scholar]
  13. Hamilton R. L., Regen D. M., Gray M. E., LeQuire V. S. Lipid transport in liver. I. Electron microscopic identification of very low density lipoproteins in perfused rat liver. Lab Invest. 1967 Feb;16(2):305–319. [PubMed] [Google Scholar]
  14. Jamieson J. D., Palade G. E. Intracellular transport of secretory proteins in the pancreatic exocrine cell. I. Role of the peripheral elements of the Golgi complex. J Cell Biol. 1967 Aug;34(2):577–596. doi: 10.1083/jcb.34.2.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jamieson J. D., Palade G. E. Intracellular transport of secretory proteins in the pancreatic exocrine cell. II. Transport to condensing vacuoles and zymogen granules. J Cell Biol. 1967 Aug;34(2):597–615. doi: 10.1083/jcb.34.2.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jones A. L., Ruderman N. B., Herrera M. G. Electron microscopic and biochemical study of lipoprotein synthesis in the isolated perfused rat liver. J Lipid Res. 1967 Sep;8(5):429–446. [PubMed] [Google Scholar]
  17. KESSEL R. G., BEAMS H. W. AN UNUSUAL CONFIGURATION OF THE GOLGI COMPLEX IN PIGMENT-PRODUCING "TEST" CELLS OF THE OVARY OF THE TUNICATE, STYELA. J Cell Biol. 1965 Apr;25:55–67. doi: 10.1083/jcb.25.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. LUFT J. H. Improvements in epoxy resin embedding methods. J Biophys Biochem Cytol. 1961 Feb;9:409–414. doi: 10.1083/jcb.9.2.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lane N. J. Distribution of phosphatases in the golgi region and associated structures of the thoracic ganglionic neurons in the grasshopper, Melanoplus differentialis. J Cell Biol. 1968 Apr;37(1):89–104. doi: 10.1083/jcb.37.1.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lombardi B. Considerations on the pathogenesis of fatty liver. Lab Invest. 1966 Jan;15(1 Pt 1):1–20. [PubMed] [Google Scholar]
  21. Lombardi B., Oler A. Choline deficiency fatty liver. Protein synthesis and release. Lab Invest. 1967 Sep;17(3):308–321. [PubMed] [Google Scholar]
  22. Lombardi B. Pathogenesis of fatty liver. Fed Proc. 1965 Sep-Oct;24(5):1200–1205. [PubMed] [Google Scholar]
  23. MANTON I. On a reticular derivative from Golgi bodies in the meristem of Anthroceros. J Biophys Biochem Cytol. 1960 Sep;8:221–231. doi: 10.1083/jcb.8.1.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. MOLLENHAUER H. H., WHALEY W. G. An observation on the functioning of the Golgi apparatus. J Cell Biol. 1963 Apr;17:222–225. doi: 10.1083/jcb.17.1.222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mahley R. W., Gray M. E., Hamilton R. L., LeQuire V. S. Lipid transport in liver. II. Electron microscopic and biochemical studies of alterations in lipoprotein transport induced by cortisone in the rabbit. Lab Invest. 1968 Oct;19(4):358–369. [PubMed] [Google Scholar]
  26. Neutra M., Leblond C. P. Radioautographic comparison of the uptake of galactose-H and glucose-H3 in the golgi region of various cells secreting glycoproteins or mucopolysaccharides. J Cell Biol. 1966 Jul;30(1):137–150. doi: 10.1083/jcb.30.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Neutra M., Leblond C. P. Synthesis of the carbohydrate of mucus in the golgi complex as shown by electron microscope radioautography of goblet cells from rats injected with glucose-H3. J Cell Biol. 1966 Jul;30(1):119–136. doi: 10.1083/jcb.30.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. REYNOLDS E. S. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963 Apr;17:208–212. doi: 10.1083/jcb.17.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rambourg A., Hernandez W., Leblond C. P. Detection of complex carbohydrates in the Golgi apparatus of rat cells. J Cell Biol. 1969 Feb;40(2):395–414. doi: 10.1083/jcb.40.2.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ruderman N. B., Richards K. C., Valles de Bourges V. Regulation of production and release of lipoprotein by the perfused rat liver. J Lipid Res. 1968 Sep;9(5):613–619. [PubMed] [Google Scholar]
  31. SABATINI D. D., BENSCH K., BARRNETT R. J. Cytochemistry and electron microscopy. The preservation of cellular ultrastructure and enzymatic activity by aldehyde fixation. J Cell Biol. 1963 Apr;17:19–58. doi: 10.1083/jcb.17.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schimke R. T., Ganschow R., Doyle D., Arias I. M. Regulation of protein turnover in mammalian tissues. Fed Proc. 1968 Sep-Oct;27(5):1223–1230. [PubMed] [Google Scholar]
  33. Schlunk F. F., Lombardi B. Liver liposomes. I. Isolation and chemical characterization. Lab Invest. 1967 Jul;17(1):30–38. [PubMed] [Google Scholar]
  34. Schlunk F. F., Longnecker D. S., Lombardi B. On the ethionine-induced inhibition of protein synthesis in male and female rats--lack of effect on intestinal mucosa. Biochim Biophys Acta. 1968 Jun 24;158(3):425–434. doi: 10.1016/0304-4165(68)90296-1. [DOI] [PubMed] [Google Scholar]
  35. Stein O., Stein Y. Lipid synthesis, intracellular transport, storage, and secretion. I. Electron microscopic radioautographic study of liver after injection of tritiated palmitate or glycerol in fasted and ethanol-treated rats. J Cell Biol. 1967 May;33(2):319–339. doi: 10.1083/jcb.33.2.319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Stein O., Stein Y. The role of the liver in the metabolism of chylomicrons, studied by electron microscopic autoradiography. Lab Invest. 1967 Oct;17(4):436–446. [PubMed] [Google Scholar]
  37. UGAZIO G., LOMBARDI B. SERUM LIPOPROTEINS IN RATS WITH ETHIONINE-INDUCED FATTY LIVER. Lab Invest. 1965 Jun;14:711–719. [PubMed] [Google Scholar]

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

RESOURCES