title: FAPPs control Golgi-to-cell-surface membrane traffic by binding to ARF and PtdIns(4)P.
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)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.
authors.affiliation: Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, via Nazionale, 66030 Santa Maria Imbaro (CH), Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Godi
authors.forename: Antonella
authors.initials: A
authors.lastname: Di Campli
authors.forename: Athanasios
authors.initials: A
authors.lastname: Konstantakopoulos
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Tullio
authors.forename: Dario R
authors.initials: DR
authors.lastname: Alessi
authors.forename: Gursant S
authors.initials: GS
authors.lastname: Kular
authors.forename: Tiziana
authors.initials: T
authors.lastname: Daniele
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Marra
authors.forename: John M
authors.initials: JM
authors.lastname: Lucocq
authors.forename: M Antonietta
authors.initials: MA
authors.lastname: De Matteis
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008969:Molecular Sequence Data; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005656:Fungal Proteins; C487037:PLEKHA3 protein, human; C487038:PLEKHA8 protein, human; D018129:Phosphatidylinositol Phosphates; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C037178:phosphatidylinositol 4-phosphate; D020727:ADP-Ribosylation Factors