title: The BAR domain protein Arfaptin-1 controls secretory granule biogenesis at the trans-Golgi network.
abstract: BAR domains can prevent membrane fission through their ability to shield necks of budding vesicles from fission-inducing factors. However, the physiological role of this inhibitory function and its regulation is unknown. Here we identify a checkpoint involving the BAR-domain-containing protein Arfaptin-1 that controls biogenesis of secretory granules at the trans-Golgi network (TGN). We demonstrate that protein kinase D (PKD) phosphorylates Arfaptin-1 at serine 132, which disrupts the ability of Arfaptin-1 to inhibit the activity of ADP ribosylation factor, an important component of the vesicle scission machinery. The physiological significance of this regulatory mechanism is evidenced by loss of glucose-stimulated insulin secretion due to granule scission defects in pancreatic β cells expressing nonphosphorylatable Arfaptin-1. Accordingly, depletion of Arfaptin-1 leads to the generation of small nonfunctional secretory granules. Hence, PKD-mediated Arfaptin-1 phosphorylation is necessary to ensure biogenesis of functional transport carriers at the TGN in regulated secretion.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM, CNRS, Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Helmuth
authors.initials: H
authors.lastname: Gehart
authors.forename: Alexander
authors.initials: A
authors.lastname: Goginashvili
authors.forename: Rainer
authors.initials: R
authors.lastname: Beck
authors.forename: Joëlle
authors.initials: J
authors.lastname: Morvan
authors.forename: Eric
authors.initials: E
authors.lastname: Erbs
authors.forename: Ivan
authors.initials: I
authors.lastname: Formentini
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: De Matteis
authors.forename: Yannick
authors.initials: Y
authors.lastname: Schwab
authors.forename: Felix T
authors.initials: FT
authors.lastname: Wieland
authors.forename: Romeo
authors.initials: R
authors.lastname: Ricci
mesh_terms: D020727:ADP-Ribosylation Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D045744:Cell Line, Tumor; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C555063:arfaptin 1, rat; D012694:Serine; C089212:protein kinase D; D011493:Protein Kinase C; D020727:ADP-Ribosylation Factors