title: AP-1 and clathrin are essential for secretory granule biogenesis in Drosophila.
abstract: Regulated secretion of hormones, digestive enzymes, and other biologically active molecules requires the formation of secretory granules. Clathrin and the clathrin adaptor protein complex 1 (AP-1) are necessary for maturation of exocrine, endocrine, and neuroendocrine secretory granules. However, the initial steps of secretory granule biogenesis are only minimally understood. Powerful genetic approaches available in the fruit fly Drosophila melanogaster were used to investigate the molecular pathway for biogenesis of the mucin-containing "glue granules" that form within epithelial cells of the third-instar larval salivary gland. Clathrin and AP-1 colocalize at the trans-Golgi network (TGN) and clathrin recruitment requires AP-1. Furthermore, clathrin and AP-1 colocalize with secretory cargo at the TGN and on immature granules. Finally, loss of clathrin or AP-1 leads to a profound block in secretory granule formation. These findings establish a novel role for AP-1- and clathrin-dependent trafficking in the biogenesis of mucin-containing secretory granules.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Ontario, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Burgess
authors.forename: Miluska
authors.initials: M
authors.lastname: Jauregui
authors.forename: Julie
authors.initials: J
authors.lastname: Tan
authors.forename: Janet
authors.initials: J
authors.lastname: Rollins
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lallet
authors.forename: Peter A
authors.initials: PA
authors.lastname: Leventis
authors.forename: Gabrielle L
authors.initials: GL
authors.lastname: Boulianne
authors.forename: Henry C
authors.initials: HC
authors.lastname: Chang
authors.forename: Roland
authors.initials: R
authors.lastname: Le Borgne
authors.forename: Helmut
authors.initials: H
authors.lastname: Krämer
authors.forename: Julie A
authors.initials: JA
authors.lastname: Brill
mesh_terms: D033961:Adaptor Protein Complex 1 / Q000378:metabolism*; D000818:Animals; D002966:Clathrin / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D021381:Protein Transport; D012469:Salivary Glands / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: D033961:Adaptor Protein Complex 1; D002966:Clathrin