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, Tiziana Daniele, Pierfrancesco Marra, John M Lucocq, M Antonietta De Matteis

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427 Citations (Scopus)


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)P(2)). 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
Issue number5
Publication statusPublished - May 2004


  • ADP-Ribosylation Factors
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Biological Transport
  • COS Cells
  • Carrier Proteins
  • Cell Membrane
  • Fungal Proteins
  • Golgi Apparatus
  • Humans
  • Molecular Sequence Data
  • Phosphatidylinositol Phosphates
  • Protein Structure, Tertiary
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • Subcellular Fractions
  • trans-Golgi Network


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