Nature Cell Biology
6, 393 - 404 (2004)
Published online: 25 April 2004; | doi:10.1038/ncb1119
FAPPs control Golgi-to-cell-surface membrane traffic by binding to ARF and PtdIns(4)PAnna Godi1, 4, Antonella Di Campli1, 4, Athanasios Konstantakopoulos2, Giuseppe Di Tullio1, Dario R. Alessi3, Gursant S. Kular3, Tiziana Daniele1, Pierfrancesco Marra1, John M. Lucocq2
& M. Antonietta De Matteis11
Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, via Nazionale, 66030 Santa Maria Imbaro (CH), Italy. 2
MSI/WTB Complex, University of Dundee, Dundee, UK. 3
Division of Cell Signalling, University of Dundee, Dundee DD1 5EH, UK. 4
These authors contributed equally to this work.
Correspondence should be addressed to M. Antonietta De Matteis dematteis@negrisud.itThe 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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