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FAPPs control Golgi-to-cell-surface membrane traffic by binding to ARF and PtdIns(4)P

Nature Cell Biology volume 6, pages 393–404 (2004)Cite this article

Abstract

The molecular mechanisms underlying the formation of carriers trafficking from the Golgi complex to the cell surface are still ill-defined; nevertheless, the involvement of a lipid-based machinery is well established. This includes phosphatidylinositol 4-phosphate (PtdIns(4)P), the precursor for phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). In yeast, PtdIns(4)P exerts a direct role, however, its mechanism of action and its targets in mammalian cells remain uncharacterized. We have identified two effectors of PtdIns(4)P, the four-phosphate-adaptor protein 1 and 2 (FAPP1 and FAPP2). Both proteins localize to the trans-Golgi network (TGN) on nascent carriers, and interact with PtdIns(4)P and the small GTPase ADP-ribosylation factor (ARF) through their plekstrin homology (PH) domain. Displacement or knockdown of FAPPs inhibits cargo transfer to the plasma membrane. Moreover, overexpression of FAPP-PH impairs carrier fission. Therefore, FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery that controls generation of constitutive post-Golgi carriers.

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Figure 1: FAPPs localize to TGN exit sites.
Figure 2: Association of FAPPs with the TGN is dependent on PtdIns(4)P and regulated by ARF.
Figure 3: FAPP-PH is necessary and sufficient for targeting FAPPs to the TGN.
Figure 4: PtdIns(4)P-dependent and PtdIns(4)P-independent targeting of FAPP-PH.
Figure 5: FAPP-PH interacts with the small GTPase ARF.
Figure 6: FAPPs are required for TGN-to-plasma membrane transport.
Figure 7: FAPPs control the formation of transport carriers at the TGN.

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Acknowledgements

We thank B. Antonny for providing reagents. We are also grateful to A. Luini, V. Malhotra, and to the members of the Golgi group of the Consorzio Mario Negri Sud for discussions. We thank C. Berrie for reading the manuscript and E. Fontana for artwork preparation. This work was supported in part by the Italian Association for Cancer Research, Telethon Italia, the European Community and the Italian Ministry of Education. A.D.C. and T.D. are supported by fellowships from the Italian Foundation of Cancer Research.

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  1. Anna Godi and Antonella Di Campli: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, via Nazionale, Santa Maria Imbaro (CH), 66030, Italy

    Anna Godi, Antonella Di Campli, Giuseppe Di Tullio, Tiziana Daniele, Pierfrancesco Marra & M. Antonietta De Matteis

  2. MSI/WTB Complex, University of Dundee, Dundee, UK

    Athanasios Konstantakopoulos & John M. Lucocq

  3. Division of Cell Signalling, University of Dundee, Dundee, DD1 5EH, UK

    Dario R. Alessi & Gursant S. Kular

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Godi, A., Campli, A., Konstantakopoulos, A. et al. FAPPs control Golgi-to-cell-surface membrane traffic by binding to ARF and PtdIns(4)P. Nat Cell Biol 6, 393–404 (2004). https://doi.org/10.1038/ncb1119

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