Abstract
The small GTPase ADP-ribosylation factor (ARF) regulates the structure and function of the Golgi complex through mechanisms that are understood only in part, and which include an ability to control the assembly of coat complexes and phospholipase D (PLD). Here we describe a new property of ARF, the ability to recruit phosphatidylinositol-4-OH kinase-β and a still unidentified phosphatidylinositol-4-phosphate-5-OH kinase to the Golgi complex, resulting in a potent stimulation of synthesis of phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate; this ability is independent of its activities on coat proteins and PLD. Phosphatidylinositol-4-OH kinase-β is required for the structural integrity of the Golgi complex: transfection of a dominant-negative mutant of the kinase markedly alters the organization of the organelle.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
De Camilli, P., Emr, S. D., McPherson, P. S. & Novick, P. Phosphoinositides as regulators in membrane traffic. Science 271, 1533–1539 (1996).
Martin, T. F. J. Phosphoinositides as spatial regulators of membrane traffic. Curr. Opin. Neurobiol. 7, 331–338 (1997).
Sheperd, P. R., Reaves, B. J. & Davidson, W. H. Phosphoinositide 3-kinases and membrane traffic. Trends Cell Biol. 6, 92–97 (1996).
Gehrmann, T. & Heilmeyer, L. M. Jr Phosphatidylinositol 4-kinases. Eur. J. Biochem. 253, 357–370 (1998).
Loijens, J. C., Boronenkov, I. V., Parker, G. J. & Anderson, R. A. The phosphatidylinositol 4-phosphate 5-kinase family. Adv. Enzyme Regul. 36, 115–140 (1996).
Herman, P. K., Stack, J. H., DeModena, J. A. & Emr, S. D. A novel protein kinase homolog essential for protein sorting to the yeast lysosome-like vacuole. Cell 64, 425–437 (1991).
Stack, J. H., Herman, P. K., Schu, P. V. & Emr, S. D. A membrane-associated complex containing the Vps15 protein kinase and the Vps34 PI 3-kinase is essential for protein sorting to the yeast lysosome-like vacuole. EMBO J. 12, 2195–2204 (1993).
Schu, P. V. et al. Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene is essential for protein sorting. Science 260, 88–91 (1993).
Jones, S. M. & Howell, K. E. Phosphatidylinositol 3-kinase is required for the formation of constitutive transport vesicles from the TGN. J. Cell Biol. 139, 339–349 (1997).
Jergil, B. & Sundler, R. Phosphorylation of phosphatidylinositol in rat liver Golgi. J. Biol. Chem. 258, 7968–7973 (1983).
Nakagawa, T., Goto, K. & Kondo H. Cloning, expression, and location of 230-kDa phosphatidylinositol 4-kinase. J. Biol.Chem. 271, 12088–12094 (1996).
Wong, K., Meyers, d. d. R., Cantley, L. C. Subcellular locations of phosphatidylinositol 4-kinase isoforms. J. Biol.Chem. 272, 13236–13241 (1997).
Godi, A. et al. ADP ribosylation factor regulates spectrin binding to the Golgi complex. Proc. Natl Acad. Sci. USA. 95, 8607–8612 (1998).
Schmid, S. L., McNiven, M. A. & De Camilli, P. Dynamin and its partners: a progress report. Curr. Opin. Cell Biol. 10, 504–512 (1998).
Brown, H. A., Gutowski, S., Moomaw, C. R., Slaughter, C. & Sternweis, P. C. ADP-ribosylation factor, a small GTP-dependent regulatory protein, stimulates phospholipase D activity. Cell 75, 1137–1144 (1993).
Cockroft, S. et al. Phospholipase D: a downstream effector of ARF in granulocytes. Science 263, 523–526 (1994).
Liscovitch, M., Chalifa, V., Pertile, P., Chen, C. S. & Cantley, L. C. Novel function of phosphatidylinositol 4,5-bisphosphate as a cofactor for brain membrane phospholipase D. J. Biol. Chem. 269, 21403–21406 (1994).
Jenkins, G. H., Fisette, P. L. & Anderson, R. A. Type I phosphatidylinositol 4-phosphate 5-kinase isoforms are specifically stimulated by phosphatidic acid. J. Biol. Chem. 269, 11547–11554 (1994).
Moritz, A., De Graan, P. N., Gispen, W. H. & Wirtz, K. W. Phosphatidic acid is a specific activator of phosphatidylinositol-4-phosphate kinase. J. Biol. Chem. 267, 7207–7210 (1992).
Fensome, A. et al. ARF and PITP restore GTP gamma S-stimulated protein secretion from cytosol-depleted HL60 cells by promoting PIP2 synthesis. Curr. Biol. 6, 730–738 (1996).
Martin, A. et al. Activation of phospholipase D and phosphatidylinositol 4-phosphate 5-kinase in HL60 membranes is mediated by endogenous Arf but not Rho. J. Biol.Chem. 271, 17397–17403 (1996).
Liscovitch, M. & Cantley, L. C. Signal transduction and membrane traffic: the PITP/phosphoinositide connection. Cell 81, 659–662 (1995).
Liscovitch, M. & Chalifa, V. in Signal Activated Phospholipases (ed. Liscovitch, M.) 31–63 (R. G. Landes, Austin, 1994).
Pike, L. G. Phosphatidylinositol 4-kinases and the role of polyphosphoinositides in cellular regulation. Endocrinol. Rev. 13, 692–706 (1992).
Endemann, G. C., Graziani, A. & Cantley, L. C. A monoclonal antibody distinguishes two types of phosphatidylinositol 4-kinase. Biochem. J. 273, 63–66 (1991).
Lee, F. J. S. et al. Characterization of class II and class III ADP-ribosylation factor genes and proteins in Drosophila melanogaster. J. Biol. Chem. 269, 21555–21560 (1994).
Donaldson, J. G., Finazzi, D. & Klausner, R. D. Brefeldin A inhibits Golgi membrane-catalysed exchange of guanine nucleotide onto ARF protein. Nature 360, 350–352 (1992).
Linstedt, A. D. & Hauri, H. P. Giantin, a novel conserved Golgi membrane protein containing a cytoplasmic domain of at least 350 kDa. Mol. Biol.Cell. 4, 679–693 (1993).
Moss, J. & Vaughan, M. Molecules in the ARF orbit. J. Biol. Chem. 273, 21431–21434 (1998).
Gaynor, E. C., Chen, C. Y., Emr, S. D. & Graham, T. R. ARF is required for maintenance of yeast Golgi and endosome structure and function. Mol. Biol. Cell. 9, 653–670 (1998).
Kauffmann-Zeh, A. et al. Requirement for phosphatidylinositol transfer protein in epidermal growth factor signaling. Science 268, 1188–1190 (1995).
Nishikawa, K. et al. Association of protein kinase Cµ with type II phosphatidylinositol 4-kinase and type I phosphatidylinositol-4-phosphate 5-kinase. J. Biol. Chem. 273, 23126–23133 (1998).
Garcia-Bustos, J. F., Marini, F., Stevenson, I., Frei, C. & Hall, M. N. PIK1, an essential phosphatidylinositol 4-kinase associated with the yeast nucleus. EMBO J. 13, 2352–2361 (1994).
Choi, J. H., Lou, W. & Vancura, A. Interaction between phosphatidylinositol 4-kinase PIK1 and phosphatidylinositol polyphosphate 5-phosphatase INP52 in Saccharomyces cerevisae. Mol. Biol. Cell. Abstr. 9, 120 (1998).
De Matteis, M. A. & Morrow, J. S. The role of ankyrin and spectrin in membrane transport and domain formation. Curr. Opin. Cell Biol. 10, 542–549 (1998).
Moss, J. et al. Soluble guanine nucleotide-dependent ADP-ribosylation factors in activation of adenylyl cyclase by cholera toxin. Methods Enzymol. 195, 243–256 (1991).
Malhotra, V., Serafini, T., Orci, L., Shepherd, J. C. & Rothman, J. E. Purification of a novel class of coated vesicles mediating biosynthetic protein transport through the Golgi stack. Cell 58, 329–336 (1989).
Orci, L. et al. Budding from Golgi membranes requires the coatomer complex of non-clathrin coat proteins. Nature 362, 648–651 (1993).
Aniento, F., Gu, F., Parton, R. G. & Gruenberg, J. An endosomal bCOP is involved in the pH-dependent formation of transport vesicles destined for late endosomes. J. Cell Biol. 133, 29–41 (1996).
Meyers, R. & Cantley, L. C. Cloning and characterization of a wortmannin-sensitive human phosphatidylinositol 4-kinase. J. Biol. Chem. 272, 4384–4390 (1997).
Falasca, M., Iurisci, C., Carvelli, A., Sacchetti, A. & Corda, D. Release of the mitogen lysophosphatidylinositol from H-Ras-transformed fibroblasts; a possible mechanism of autocrine control of cell proliferation. Oncogene 16, 2357–2365 (1998).
Fullekrug, J. et al. CaBP1, a calcium binding protein of the thioredoxin family, is a resident KDEL protein of the ER and not of the intermediate compartment. J. Cell Sci. 107, 2719–2727 (1994).
Margolis, R. N., Taylor, S. I., Seminara, D. & Hubbard, A. L. Identification of pp120, an endogenous substrate for the hepatocyte insulin receptor tyrosine kinase, as an integral membrane glycoprotein of the bile canalicular domain. Proc. Natl Acad. Sci. USA 85, 7256–7259 (1988).
Acknowledgements
We thank C. Walch-Solimena and P. Novick for sharing unpublished results; J. Backer, R. Kahn, P. Hauri and F. Wieland for antibodies; J. Moss for the Drosophila ARFIII complementary DNA; M. Falasca for discussions; and C.P. Berrie for critical reading of the manuscript. This work was supported in part by grants from Telethon (E732), the Human Frontier Science Program (to M.A.D.M.), the Italian National Research Council (97.01300. PF49 and 97.01305.PF49) and the Italian Association for Cancer Research. A.G. and P.P. received fellowships from the Centro di Formazione e Studi per il Mezzogiorno (FORMEZ) and Banca di Roma, respectively.
Correspondence and requests for materials should be addressed to M.A.D.M.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Godi, A., Pertile, P., Meyers, R. et al. ARF mediates recruitment of PtdIns-4-OH kinase-β and stimulates synthesis of PtdIns(4,5)P2 on the Golgi complex. Nat Cell Biol 1, 280–287 (1999). https://doi.org/10.1038/12993
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/12993
This article is cited by
-
It started with a western
Nature Cell Biology (2024)
-
Phosphoinositides as membrane organizers
Nature Reviews Molecular Cell Biology (2022)
-
ACBD3 modulates KDEL receptor interaction with PKA for its trafficking via tubulovesicular carrier
BMC Biology (2021)
-
A Golgi-derived vesicle potentiates PtdIns4P to PtdIns3P conversion for endosome fission
Nature Cell Biology (2021)
-
Dopey1-Mon2 complex binds to dual-lipids and recruits kinesin-1 for membrane trafficking
Nature Communications (2019)