AP-1 and clathrin are essential for secretory granule biogenesis in Drosophila

• Published in: Molecular biology of the cell Vol. 22; no. 12; pp. 2094 - 2105
• Main Authors: Burgess, Jason, Jauregui, Miluska, Tan, Julie, Rollins, Janet, Lallet, Sylvie, Leventis, Peter A, Boulianne, Gabrielle L, Chang, Henry C, Le Borgne, Roland, Krämer, Helmut, Brill, Julie A
• Format: Journal Article
• Language: English
• Published: United States American Society for Cell Biology 15.06.2011; The American Society for Cell Biology
• Subjects: Adaptor Protein Complex 1; Adaptor Protein Complex 1 - metabolism; Animals; Cellular Biology; Clathrin; Clathrin - metabolism; Drosophila melanogaster; Drosophila melanogaster - metabolism; Epithelial Cells; Epithelial Cells - metabolism; Golgi Apparatus; Golgi Apparatus - metabolism; Life Sciences; Microscopy, Electron; Microscopy, Fluorescence; Polymerase Chain Reaction; Protein Transport; Salivary Glands; Salivary Glands - metabolism; Secretory Vesicles; Secretory Vesicles - metabolism; trans-Golgi Network; trans-Golgi Network - metabolism
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E11-01-0054

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.