The Role of the Phosphatidylinositol Cycle in the Activation of the Frog Egg

  • Richard Nuccitelli
  • James Ferguson
  • Jin-Kwan Han


Over the past five years we have filled in many steps in the sequence of events responsible for the activation of both vertebrate and invertebrate eggs. While the egg of the sea urchin has been the most popular system for the study of gamete activation, several investigators have been studying vertebrate eggs as well. The amphibian egg has emerged as the best studied vertebrate model to date. We now know that the activation events following normal fertilization in this egg include the phosphatidylinositol lipid cascade. We will review some of these recent observations here and will then concentrate on current studies from our laboratory that indicate a possible role for at least two of the phosphoinositols in the cascade.


Inositol Trisphosphate Cortical Granule Quiescent Period Fertilization Potential Animal Hemisphere 
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. Acott, R. S. and D. W. Carr. 1984. Inhibition of bovine spermatozoa by caudal epididymal fluid 2. Interaction of pH and a quiescent factor. Biol. Reprod. 30: 926–935.PubMedCrossRefGoogle Scholar
  2. Balla, T., G. Guillemette, A. J. Baukal, and K. J. Catt. 1987. Metabolism of inositol 1,3,4-trisphosphate to a new tetrakisphosphate isomer in angiotensin-stimulated adrenal glomerulosa cells. J. Biol. Chem. 263: 9952–9955.Google Scholar
  3. Berridge, M. J. 1987. Inositol trisphosphate and diacylglycerol: Two interacting second messengers. Annu. Rev. Biochem. 56: 159–193.PubMedCrossRefGoogle Scholar
  4. Busa, W. B. 1986. Measuring intracellular free Ca with single- and double-barreled ion-specific microelectrodes. Prog. Clin. Biol. Res. 210: 57–70.PubMedGoogle Scholar
  5. Busa, W. B. and J. H. Crowe. 1983. Intracellular pH regulates transitions between dormancy and development of brine shrimp (Artemia salira) embryos. Science 221: 366–368.PubMedCrossRefGoogle Scholar
  6. Busa, W. B. and R. Nuccitelli. 1984. Metabolic regulation via intracellular pH. Am. J. Physiol. 246: R409–438.PubMedGoogle Scholar
  7. Busa, W. B. and R. Nuccitelli. 1985. An elevated free cytosolic Ca’ wave follows fertilization in eggs of the frog, Xenopus laevis. J. Cell Biol. 100: 1325–1329.CrossRefGoogle Scholar
  8. Busa, W. B., J. E. Ferguson, S. K. Joseph, J. R. Williamson, and R. Nuccitelli. 1985. Activation of frog (Xenopus laevis) eggs by inositol trisphosphate. I. Characterization of Ca release from intracellular stores. J. Cell Biol. 101: 677–682.PubMedCrossRefGoogle Scholar
  9. Campanella, C. and P. Andreuccetti. 1977. Ultrastructural observation on cortical endoplasmic reticulum and on residual cortical granules in the egg of Xenopus laevis. Dev. Biol. 56: 110.CrossRefGoogle Scholar
  10. Campanella, C., P. Andreuccetti, C. Taddei, and R. Talevi. 1984. The modifications of cortical endoplasmic reticulum during in vitro maturation of Xenopus laevis oocytes and its involvement in cortical granule exocytosis. J. Exp. Zool. 229: 283–293.PubMedCrossRefGoogle Scholar
  11. Chambers, E. L., B. C. Pressman, and B. Rose. 1974. The activation of sea urchin eggs by the divalent ionophores A23187 and X-537A. Biochem. Biophys. Res. Commun. 60: 126–132.PubMedCrossRefGoogle Scholar
  12. Charbonneau, M. and R. D. Grey. 1984. The onset of activation responsiveness during maturation coincides with the formation of the cortical endoplasmic reticulum in oocytes. of Xenopus laevis. Dev. Biol. 102: 90–97.CrossRefGoogle Scholar
  13. Christen, R., R. W. Schackmann, and B. M. Shapiro. 1982. Elevation of the intracellular pH activates respiration and motility of sperm of the sea urchin. J. Biol. Chem. 91: 174a.Google Scholar
  14. Crossley, I., K. Swann, E. Chambers, and M. Whitaker. 1988. Activation of sea urchin eggs by inositol phosphates is independent of external calcium. Biochem. J. 252: 257–262.PubMedGoogle Scholar
  15. Cuthbertson, K. S. R., and P. H. Cobbold. 1985. Phorbol ester and sperm activate mouse oocytes by inducing sustained oscillations in cell CaZ’. Nature (Lond.) 316: 541–542.CrossRefGoogle Scholar
  16. Cuthbertson, K. S. R., D. G. Whittingham, and P. H. Cobbold. 1981. Free Ca’ increases in exponential phases during mouse oocyte activation. Nature (Gond.) 294: 754–757.CrossRefGoogle Scholar
  17. Dalcq, A. 1928. Les Bases Physiologiques de la Fecondation et de la Parthenogenese. Preses Univ. de France, Paris.Google Scholar
  18. Eisen, A. and G. T. Reynolds. 1984. Calcium transients during early development in single starfish (Asterias forbesi) oocytes. J. Cell Biol. 99: 1878–1882.PubMedCrossRefGoogle Scholar
  19. Eisen, A., D. P. Kiehart, S. J. Wieland, and G. T. Reynolds. 1984. Temporal sequence and spatial distribution of early events of fertilization in single sea urchin eggs. J. Cell Biol. 99: 1647–1654.PubMedCrossRefGoogle Scholar
  20. Gardiner, D. M. and R. D. Grey. 1983. Membrane junctions in Xenopus eggs: Their distribution suggests a role in calcium regulation. J. Cell Biol. 96: 1159–1163.PubMedCrossRefGoogle Scholar
  21. Gilkey, J. C., L. F. Jaffe, E. B. Ridgway, and G. T. Reynolds. 1978. A free calcium wave traverses the activating egg of the medaka, Ory_ias latipes. J. Cell Biol. 76: 448–466.CrossRefGoogle Scholar
  22. Grey, R. D., M. J. Bastiani, D. J. Webb, and E. R. Schertel. 1982. An electrical block is required to prevent polyspermy in eggs fertilized by natural mating of Xenopus laevis. Dev. Biol. 89: 475–484.CrossRefGoogle Scholar
  23. Hamaguchi, M. S. 1982. The role of intracellular pH in fertilization of sand dollar eggs analyzed by microinjection method, Dev. Growth & Differ. 24: 443–451.CrossRefGoogle Scholar
  24. Irvine, R. F. and R. M. Moor. 1986. Microinjection of inositol 1,3,4,5-tetrakisphosphate activates sea urchin eggs by a mechanism dependent on external Ca’. Biochem. J. 240: 917–920.PubMedGoogle Scholar
  25. Irvine, R. F. and R. M. Moor. 1987. inositol (1,3,4,5) tetrakisphosphate-induced activation of sea urchin eggs requires the presence of inositol trisphosphate. Biochem. Biophys. Res. Commun. 146: 284–290.Google Scholar
  26. Irvine, R. F., K. D. Brown, and M. J. Berridge. 1984. Specificity of inositol trisphosphate-induced calcium release from permeabilized Swiss 3T3 cells. Biochem. J. 222: 269–272.PubMedGoogle Scholar
  27. Irvine, R. F., A. J. Letcher, J. P. Heslop, and M. J. Berridge. 1986. The inositol tris/tetrakisphosphate pathway-demonstration of Ins(1,4,5)P3 3-kinase activity in animal tissues. Nature (Loud.) 320: 631–634.CrossRefGoogle Scholar
  28. Johnson, C. H. and D. Epel. 1981. Intracellular pH of sea urchin eggs measured by the dimethyloxazolidinedione (DMO) method. J. Cell Biol. 89: 284–291.PubMedCrossRefGoogle Scholar
  29. Kline, D. 1988. Calcium-dependent events at fertilization of the frog egg: injection of a calcium buffer blocks ion channel opening, exocytosis, and formation of pronuclei. Dev. Biol. 126: 346–361.PubMedCrossRefGoogle Scholar
  30. Kline, D. and L. A. Jaffe. 1987. The fertilization potential of the Xenopus egg is blocked by injection of a calcium buffer and is mimicked by injection of a GTP analog. Biophys. J. 51: 398a.Google Scholar
  31. Kline, D. and R. Nuccitelli. 1985. The wave of activation current in the Xenopus egg. Dev. Biol. 111: 471–487.PubMedCrossRefGoogle Scholar
  32. Kubota, H. Y., Y. Yoshimoto, M. Yoneda, and Y. Hiramoto. 1987. Free calcium wave upon activation in Xenopus eggs. Dev. Biol. 119: 129–136.PubMedCrossRefGoogle Scholar
  33. Lee, H. C., C. Johnson, and D. Epel. 1983. Changes in internal pH associated with initiation of motility and acrosome reaction of sea urchin sperm. Dev. Biol. 95: 31–45.PubMedCrossRefGoogle Scholar
  34. Levy, S. and A. Fein. 1985. Relationship between light sensitivity and intracellular free Ca concentration in Limulus ventral photoreceptors: A quantitative study using Ca-selective microelectrodes. J. Gen. Physiol. 85: 805–841.PubMedCrossRefGoogle Scholar
  35. Loeb, J. 1913. Artificial Parthenogenesis and Fertilization. Univ. of Chicago Press, Chicago.Google Scholar
  36. Mazia, D. 1937. The release of calcium in Arbacia eggs on fertilization. J. Cell. Comp. Phys. 10:291–304Google Scholar
  37. Miledi, R. and I. Parker. 1984. Chloride current induced by injection of calcium into Xenopus oocytes. J. Physiol. 357: 173–183.PubMedGoogle Scholar
  38. Miyazaki, S., N. Hashimoto, Y. Yoshimoto, T. Kishimoto, Y. Igusa, and Y. Hiramoto. 1986. Temporal and spatial dynamics of the periodic increase in intracellular free calcium at fertilization of golden hamster eggs. Dev. Biol. 118: 259–267.PubMedCrossRefGoogle Scholar
  39. Nishioka, D. and N. Cross. 1978. The role of external sodium in sea urchin fertilization. p.403–413. In: Cell Reproduction: In Honor of Daniel Mazia. E. R. Dirkson, D. M. Prescott and C. F. Fox (Eds.). Academic Press, New York.Google Scholar
  40. Nuccitelli, R. 1987. The wave of activation current in the egg of the medaka fish. Dev. Biol. 122: 522–534.PubMedCrossRefGoogle Scholar
  41. Nuccitelli, R., D. J. Webb, S. T. Lagier, and G. B. Matson. 1981. 31P NMR reveals increased intracellular pH after fertilization in Xenopus eggs. Proc. Natl. Acad. Sci. USA 78: 4421–4425.Google Scholar
  42. Nuccitelli, R., D. Kline, W. B. Busa, R. Talevi, and C. Campanella. 1988. A highly localized activation current yet widespread intracellular calcium increase in the egg of the frog, Discoglossus pictus. Dev. Biol. 130 (In press).Google Scholar
  43. Oron, Y., N. Dascal, E. Nadler, and M. Lupu. 1985. Inositol 1,4,5-trisphosphate mimics muscarinic response in Xenopus oocytes. Nature (Loud.) 313: 141–143.CrossRefGoogle Scholar
  44. Parker, I. and R. Miledi. 1987. Injection of inositol 1,3,4,5-tetrakisphosphate into Xenopus oocytes generates a chloride current dependent upon intracellular calcium. Proc. R. Soc. Loud. B. 232: 59–70.CrossRefGoogle Scholar
  45. Pasteels, J. 1938. The role of calcium in the activation of the egg of the mollusk. Wimereux Stn. Zool. Travaux. 13: 515–530.Google Scholar
  46. Poenie, M., J. Alderton, R. Steinhardt, and R. Tsien. 1986. Calcium rises abruptly and briefly throughout the cell at the onset of anaphase. Science 233: 886–889.PubMedCrossRefGoogle Scholar
  47. Purves, R. D. 1981. Microelectrode methods for intracellular recording and ionotophoresis. Academic Press, London.Google Scholar
  48. Ridgway, E. B., J. C. Gilkey, and L. F. Jaffe. 1977. Free calcium increases explosively in activating medaka eggs. Proc. Natl. Acad. Sci. USA 74: 623–627.PubMedCrossRefGoogle Scholar
  49. Robinson, K. R. 1979. Electrical currents through full-grown and maturing Xenopus oocytes. Proc. Natl. Acad. Sci. USA 76: 837–841.PubMedCrossRefGoogle Scholar
  50. Schackmann, R. W. and B. M. Shapiro. 1981. A partial sequence of ionic changes associated with the acrosome reaction of Strongylocentrotus purpuratus. Dev. Biol. 81: 145–154.CrossRefGoogle Scholar
  51. Shears, S. B., J. B. Parry, E. K. Y. Tang, R. F. Irvine, R. H. Michell, and C. J. Kirk. 1987a. Metabolism of D-myo-inositol 1,3,4,5-tetrakisphosphate by rat liver, including the synthesis of a novel isomer of myo-inositol tetrakisphosphate. Biochem. J. 246: 139–147.PubMedGoogle Scholar
  52. Shears, S. B., C. J. Kirk, and R. H. Michell. 1987b. The pathway of myo-inositol 1,3,4-trisphosphate dephosphorylation in liver. Biochem. J. 248: 977–980.PubMedGoogle Scholar
  53. Shen, S. S. and R. A. Steinhardt. 1978. Direct measurement of intracellular pH during metabolic derepression of the sea urchin egg. Nature (Lond.) 272: 253–254.CrossRefGoogle Scholar
  54. Steinhardt, R. A. and D. Epel. 1974. Activation of sea urchin eggs by a calcium ionophore. Proc. Natl. Acad. Sci. USA 71: 1915–1919.PubMedCrossRefGoogle Scholar
  55. Steinhardt, R. A., D. Epel, and E. J. Carroll Jr. 1974. Is calcium ionophore a universal activator for unfertilized eggs? Nature (Lond.) 252: 41–43.CrossRefGoogle Scholar
  56. Swann, K. and M. Whitaker 1986. The part played by inositol trisphosphate and calcium in the propagation of the fertilization wave in sea urchin eggs. J. Cell Biol. 103: 2333–2342.PubMedCrossRefGoogle Scholar
  57. Tilney, L. G. 1976. The polymerization of actin. III. Aggregates of nonfilamentous actin and its associated proteins: a storage form of actin. J. Cell Biol. 69: 73–89.PubMedCrossRefGoogle Scholar
  58. Tilney, L. G., D. P. Kiehart, C. Sardet, and M. Tilney. 1978. Polymerization of actin. IV. Role of Ca’ and H` in the assembly of actin and in membrane fusion in the acrosomal reaction of echinoderm sperm. J. Cell. Biol. 77: 536–550.PubMedCrossRefGoogle Scholar
  59. Traynor-Kaplan, A. E., A. L. Harris, B. L. Thompson, P. Taylor, and L. A. Skylar. 1988. An inositol tetrakisphosphate-containing phospholipid in activated neutrophils. Nature (Lond.) 334: 353–356.CrossRefGoogle Scholar
  60. Webb, D. J. and R. Nuccitelli. 1981. Direct measurement of intracellular pH changes in Xenopus eggs at fertilization and cleavage. J. Cell Biol. 91: 562–567.PubMedCrossRefGoogle Scholar
  61. Webb, D. J. and R. Nuccitelli. 1982. Intracellular pH changes accompany the activation of development in frog eggs: comparison of pH microelectrode and 31P-NMR measurements. p. 293–324. In: Intracellular pH, Its Measurement, Regulation, and Utilization in Cellular Functions. R. Nuccitelli and D. W. Deamer (Eds.). Alan R. Liss, New York.Google Scholar
  62. Winkler, M. M., R. A. Steinhardt, J. L. Grainger, and L. Minning. 1980. Dual ionic controls for the activation of protein synthesis at fertilization. Nature (Lond.) 287: 558–560.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Richard Nuccitelli
    • 1
  • James Ferguson
    • 1
  • Jin-Kwan Han
    • 1
  1. 1.Department of ZoologyUniversity of California, DavisDavisUSA

Personalised recommendations