Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 2002 Apr 15;363(Pt 2):289–295. doi: 10.1042/0264-6021:3630289

Regulation and recruitment of phosphatidylinositol 4-kinase on immature secretory granules is independent of ADP-ribosylation factor 1.

Christina Panaretou 1, Sharon A Tooze 1
PMCID: PMC1222477  PMID: 11931656

Abstract

Heterotrimeric G-proteins, as well as small GTPases of the Rho and ADP-ribosylation factor (ARF) family, are implicated in the regulation of lipid kinases, including PtdIns 4-kinases and PtdIns(4)P 5-kinases. Here, we describe a PtdIns 4-kinase activity on immature secretory granules (ISGs), regulated secretory organelles formed from the trans-Golgi network (TGN), and investigate the regulation of PtdIns4P levels on these membranes. Over 50% of the PtdIns 4-kinase activity on ISGs is inhibited by both a low concentration of adenosine and the monoclonal antibody 4C5G, a specific inhibitor of the type II PtdIns 4-kinase. Treatment of ISGs with mastoparan 7 (M7) stimulates the type II PtdIns 4-kinase via pertussis-toxin-sensitive G(i)/G(0) proteins, which, in contrast with previous results obtained with chromaffin granules [Gasman, Chasserot-Golaz, Hubert, Aunis and Bader (1998) J. Biol. Chem. 273, 16913-16920], does not require Rho A, B or C. M7 treatment also leads to an inhibition in the recruitment of ARF to ISG membranes: this inhibition is not dependent on G(i)/G(0) activation, and is not linked to the stimulation of PtdIns 4-kinase observed with M7. PtdIns 4-kinase activity on ISGs is not regulated by myristoylated ARF1-GTP, in contrast with results obtained with Golgi membranes [Godi, Pertile, Meyers, Marra, Di Tullio, Iurisci, Luini, Corda and De Matteis (1999) Nat. Cell Biol. 1, 280-287; Jones, Morris, Morgan, Kondo, Irvine and Cockcroft (2000) J. Biol. Chem. 275, 13962-13170], whereas ARF1-GTP does regulate the production of PtdIns(4,5)P(2). Our results suggest that the regulation of PtdIns 4-kinase on the ISGs differs in comparison with that on the TGN, and might be related to a specific requirement of ISG maturation.

Full Text

The Full Text of this article is available as a PDF (357.2 KB).

Selected References

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

  1. Aktories K., Just I. In vitro ADP-ribosylation of Rho by bacterial ADP-ribosyltransferases. Methods Enzymol. 1995;256:184–195. doi: 10.1016/0076-6879(95)56023-8. [DOI] [PubMed] [Google Scholar]
  2. Austin C., Hinners I., Tooze S. A. Direct and GTP-dependent interaction of ADP-ribosylation factor 1 with clathrin adaptor protein AP-1 on immature secretory granules. J Biol Chem. 2000 Jul 21;275(29):21862–21869. doi: 10.1074/jbc.M908875199. [DOI] [PubMed] [Google Scholar]
  3. Barr F. A., Huttner W. B. A role for ADP-ribosylation factor 1, but not COP I, in secretory vesicle biogenesis from the trans-Golgi network. FEBS Lett. 1996 Apr 8;384(1):65–70. doi: 10.1016/0014-5793(96)00285-2. [DOI] [PubMed] [Google Scholar]
  4. Barylko B., Gerber S. H., Binns D. D., Grichine N., Khvotchev M., Südhof T. C., Albanesi J. P. A novel family of phosphatidylinositol 4-kinases conserved from yeast to humans. J Biol Chem. 2001 Jan 19;276(11):7705–7708. doi: 10.1074/jbc.C000861200. [DOI] [PubMed] [Google Scholar]
  5. Cremona O., De Camilli P. Phosphoinositides in membrane traffic at the synapse. J Cell Sci. 2001 Mar;114(Pt 6):1041–1052. doi: 10.1242/jcs.114.6.1041. [DOI] [PubMed] [Google Scholar]
  6. Dittie A. S., Hajibagheri N., Tooze S. A. The AP-1 adaptor complex binds to immature secretory granules from PC12 cells, and is regulated by ADP-ribosylation factor. J Cell Biol. 1996 Feb;132(4):523–536. doi: 10.1083/jcb.132.4.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Endemann G. C., Graziani A., Cantley L. C. A monoclonal antibody distinguishes two types of phosphatidylinositol 4-kinase. Biochem J. 1991 Jan 1;273(Pt 1):63–66. doi: 10.1042/bj2730063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fruman D. A., Meyers R. E., Cantley L. C. Phosphoinositide kinases. Annu Rev Biochem. 1998;67:481–507. doi: 10.1146/annurev.biochem.67.1.481. [DOI] [PubMed] [Google Scholar]
  9. Gasman S., Chasserot-Golaz S., Hubert P., Aunis D., Bader M. F. Identification of a potential effector pathway for the trimeric Go protein associated with secretory granules. Go stimulates a granule-bound phosphatidylinositol 4-kinase by activating RhoA in chromaffin cells. J Biol Chem. 1998 Jul 3;273(27):16913–16920. doi: 10.1074/jbc.273.27.16913. [DOI] [PubMed] [Google Scholar]
  10. Godi A., Pertile P., Meyers R., Marra P., Di Tullio G., Iurisci C., Luini A., Corda D., De Matteis M. A. ARF mediates recruitment of PtdIns-4-OH kinase-beta and stimulates synthesis of PtdIns(4,5)P2 on the Golgi complex. Nat Cell Biol. 1999 Sep;1(5):280–287. doi: 10.1038/12993. [DOI] [PubMed] [Google Scholar]
  11. Goldberg J. Structural basis for activation of ARF GTPase: mechanisms of guanine nucleotide exchange and GTP-myristoyl switching. Cell. 1998 Oct 16;95(2):237–248. doi: 10.1016/s0092-8674(00)81754-7. [DOI] [PubMed] [Google Scholar]
  12. Higashijima T., Uzu S., Nakajima T., Ross E. M. Mastoparan, a peptide toxin from wasp venom, mimics receptors by activating GTP-binding regulatory proteins (G proteins). J Biol Chem. 1988 May 15;263(14):6491–6494. [PubMed] [Google Scholar]
  13. Hori Y., Demura M., Iwadate M., Ulrich A. S., Niidome T., Aoyagi H., Asakura T. Interaction of mastoparan with membranes studied by 1H-NMR spectroscopy in detergent micelles and by solid-state 2H-NMR and 15N-NMR spectroscopy in oriented lipid bilayers. Eur J Biochem. 2001 Jan;268(2):302–309. doi: 10.1046/j.1432-1033.2001.01880.x. [DOI] [PubMed] [Google Scholar]
  14. Jones D. H., Morris J. B., Morgan C. P., Kondo H., Irvine R. F., Cockcroft S. Type I phosphatidylinositol 4-phosphate 5-kinase directly interacts with ADP-ribosylation factor 1 and is responsible for phosphatidylinositol 4,5-bisphosphate synthesis in the golgi compartment. J Biol Chem. 2000 May 5;275(18):13962–13966. doi: 10.1074/jbc.c901019199. [DOI] [PubMed] [Google Scholar]
  15. Klenchin V. A., Martin T. F. Priming in exocytosis: attaining fusion-competence after vesicle docking. Biochimie. 2000 May;82(5):399–407. doi: 10.1016/s0300-9084(00)00208-x. [DOI] [PubMed] [Google Scholar]
  16. Ktistakis N. T., Linder M. E., Roth M. G. Action of brefeldin A blocked by activation of a pertussis-toxin-sensitive G protein. Nature. 1992 Mar 26;356(6367):344–346. doi: 10.1038/356344a0. [DOI] [PubMed] [Google Scholar]
  17. Leyte A., Barr F. A., Kehlenbach R. H., Huttner W. B. Multiple trimeric G-proteins on the trans-Golgi network exert stimulatory and inhibitory effects on secretory vesicle formation. EMBO J. 1992 Dec;11(13):4795–4804. doi: 10.1002/j.1460-2075.1992.tb05585.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Martin T. F. PI(4,5)P(2) regulation of surface membrane traffic. Curr Opin Cell Biol. 2001 Aug;13(4):493–499. doi: 10.1016/s0955-0674(00)00241-6. [DOI] [PubMed] [Google Scholar]
  19. Mayer A., Scheglmann D., Dove S., Glatz A., Wickner W., Haas A. Phosphatidylinositol 4,5-bisphosphate regulates two steps of homotypic vacuole fusion. Mol Biol Cell. 2000 Mar;11(3):807–817. doi: 10.1091/mbc.11.3.807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Minogue S., Anderson J. S., Waugh M. G., dos Santos M., Corless S., Cramer R., Hsuan J. J. Cloning of a human type II phosphatidylinositol 4-kinase reveals a novel lipid kinase family. J Biol Chem. 2001 Feb 13;276(20):16635–16640. doi: 10.1074/jbc.M100982200. [DOI] [PubMed] [Google Scholar]
  21. Niehrs C., Huttner W. B. Purification and characterization of tyrosylprotein sulfotransferase. EMBO J. 1990 Jan;9(1):35–42. doi: 10.1002/j.1460-2075.1990.tb08077.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Osborne S. L., Meunier F. A., Schiavo G. Phosphoinositides as key regulators of synaptic function. Neuron. 2001 Oct 11;32(1):9–12. doi: 10.1016/s0896-6273(01)00455-x. [DOI] [PubMed] [Google Scholar]
  23. Schwaninger R., Plutner H., Bokoch G. M., Balch W. E. Multiple GTP-binding proteins regulate vesicular transport from the ER to Golgi membranes. J Cell Biol. 1992 Dec;119(5):1077–1096. doi: 10.1083/jcb.119.5.1077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tooze S. A., Huttner W. B. Cell-free protein sorting to the regulated and constitutive secretory pathways. Cell. 1990 Mar 9;60(5):837–847. doi: 10.1016/0092-8674(90)90097-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tooze S. A., Martens G. J., Huttner W. B. Secretory granule biogenesis: rafting to the SNARE. Trends Cell Biol. 2001 Mar;11(3):116–122. doi: 10.1016/s0962-8924(00)01907-3. [DOI] [PubMed] [Google Scholar]
  26. Weidman P. J., Winter W. M. The G protein-activating peptide, mastoparan, and the synthetic NH2-terminal ARF peptide, ARFp13, inhibit in vitro Golgi transport by irreversibly damaging membranes. J Cell Biol. 1994 Dec;127(6 Pt 2):1815–1827. doi: 10.1083/jcb.127.6.1815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wendler F., Page L., Urbé S., Tooze S. A. Homotypic fusion of immature secretory granules during maturation requires syntaxin 6. Mol Biol Cell. 2001 Jun;12(6):1699–1709. doi: 10.1091/mbc.12.6.1699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Whitman M., Kaplan D. R., Schaffhausen B., Cantley L., Roberts T. M. Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation. Nature. 1985 May 16;315(6016):239–242. doi: 10.1038/315239a0. [DOI] [PubMed] [Google Scholar]
  29. Wiedemann C., Schäfer T., Burger M. M. Chromaffin granule-associated phosphatidylinositol 4-kinase activity is required for stimulated secretion. EMBO J. 1996 May 1;15(9):2094–2101. [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES