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

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.
Mesh Terms:
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
Nat. Cell Biol.
Date: May. 01, 2004
Download Curated Data For This Publication
323
Switch View:
  • Interactions 1