title: Recruitment of arfaptins to the trans-Golgi network by PI(4)P and their involvement in cargo export.
abstract: The BAR (Bin/Amphiphysin/Rvs) domain proteins arfaptin1 and arfaptin2 are localized to the trans-Golgi network (TGN) and, by virtue of their ability to sense and/or generate membrane curvature, could play an important role in the biogenesis of transport carriers. We report that arfaptins contain an amphipathic helix (AH) preceding the BAR domain, which is essential for their binding to phosphatidylinositol 4-phosphate (PI(4)P)-containing liposomes and the TGN of mammalian cells. The binding of arfaptin1, but not arfaptin2, to PI(4)P is regulated by protein kinase D (PKD) mediated phosphorylation at Ser100 within the AH. We also found that only arfaptin1 is required for the PKD-dependent trafficking of chromogranin A by the regulated secretory pathway. Altogether, these findings reveal the importance of PI(4)P and PKD in the recruitment of arfaptins at the TGN and their requirement in the events leading to the biogenesis of secretory storage granules.
authors.affiliation: Centre for Genomic Regulation (CRG), Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Cruz-Garcia
authors.forename: Maria
authors.initials: M
authors.lastname: Ortega-Bellido
authors.forename: Margherita
authors.initials: M
authors.lastname: Scarpa
authors.forename: Julien
authors.initials: J
authors.lastname: Villeneuve
authors.forename: Marko
authors.initials: M
authors.lastname: Jovic
authors.forename: Marc
authors.initials: M
authors.lastname: Porzner
authors.forename: Tamas
authors.initials: T
authors.lastname: Balla
authors.forename: Thomas
authors.initials: T
authors.lastname: Seufferlein
authors.forename: Vivek
authors.initials: V
authors.lastname: Malhotra
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D019556:COS Cells; D002522:Chlorocebus aethiops; D004331:Drosophila melanogaster; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes; D018129:Phosphatidylinositol Phosphates / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021601:trans-Golgi Network / Q000235:genetics / Q000378:metabolism*
chemical_list: C105088:ARFIP1 protein, human; C101158:ARFIP2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D008081:Liposomes; D018129:Phosphatidylinositol Phosphates; C089212:protein kinase D; D011493:Protein Kinase C