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ARF mediates recruitment of PtdIns-4-OH kinase-β and stimulates synthesis of PtdIns(4,5)P2 on the Golgi complex

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.

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Figure 1: ARF increases PtdIns(4)P and PtdIns(4,5)P2 levels in Golgi membranes in a cytosol-dependent manner.
Figure 2: ARF stimulates PtdIns(4)P and PtdIns(4,5)P2 synthesis.
Figure 3: Phosphatidic acid does not mediate the ARF-induced stimulation of PtdIns(4,5)P2 synthesis.
Figure 4: ARF recruits PtdIns-4-OH kinase and PtdIns(4)P-5-OH kinase to Golgi membranes.
Figure 5: PI4Kβ associates with the Golgi complex in an ARF-dependent manner.
Figure 6: PI4Kβ activity is required to create and maintain the structural integrity of the Golgi complex.

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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We thank C. Walch-Solimena and P. Novick for sharing unpublished results; J. Backer, R. Kahn, P. Hauri and F. Wieland for antibodies; J. Moss for the Drosophila ARFIII complementary DNA; M. Falasca for discussions; and C.P.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.

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Correspondence to Maria Antonietta De Matteis.

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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

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