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

Anna Godi, Antonella Di Campli, Athanasios Konstantakopoulos, Giuseppe Di Tullio, Dario R. Alessi, Gursant S. Kular, Tiziani Daniele, Pierfrancesco Marra, John M. Lucocq, M. Antonietta De Matteis

Research output: Contribution to journalArticlepeer-review

434 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)393-404
Number of pages12
JournalNature Cell Biology
Volume6
Issue number5
DOIs
Publication statusPublished - May 2004
Externally publishedYes

Bibliographical note

Funding Information:
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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