The clathrin adaptor Gga2p is a phosphatidylinositol 4-phosphate effector at the Golgi exit

• Published in: Molecular biology of the cell 2008-05, Vol.19 (5), p.1991-2002
• Main Authors: Demmel, Lars, Gravert, Maike, Ercan, Ebru, Habermann, Bianca, Müller-Reichert, Thomas, Kukhtina, Viktoria, Haucke, Volker, Baust, Thorsten, Sohrmann, Marc, Kalaidzidis, Yannis, Klose, Christian, Beck, Mike, Peter, Matthias, Walch-Solimena, Christiane
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 4-Kinase - metabolism; Adaptor Proteins, Vesicular Transport - chemistry; Adaptor Proteins, Vesicular Transport - metabolism; ADP-Ribosylation Factors - metabolism; Amino Acid Sequence; Clathrin - metabolism; Genome, Fungal - genetics; Golgi Apparatus - metabolism; Golgi Apparatus - ultrastructure; Kinetics; Models, Molecular; Molecular Sequence Data; Mutation - genetics; Phenotype; Phosphatidylinositol Phosphates - metabolism; Protein Binding; Protein Structure, Tertiary; Protein Transport; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae - ultrastructure; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - metabolism; trans-Golgi Network - metabolism; trans-Golgi Network - ultrastructure; Vacuoles - metabolism
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E06-10-0937

Phosphatidylinositol 4-phosphate (PI(4)P) is a key regulator of membrane transport required for the formation of transport carriers from the trans-Golgi network (TGN). The molecular mechanisms of PI(4)P signaling in this process are still poorly understood. In a search for PI(4)P effector molecules, we performed a screen for synthetic lethals in a background of reduced PI(4)P and found the gene GGA2. Our analysis uncovered a PI(4)P-dependent recruitment of the clathrin adaptor Gga2p to the TGN during Golgi-to-endosome trafficking. Gga2p recruitment to liposomes is stimulated both by PI(4)P and the small GTPase Arf1p in its active conformation, implicating these two molecules in the recruitment of Gga2p to the TGN, which ultimately controls the formation of clathrin-coated vesicles. PI(4)P binding occurs through a phosphoinositide-binding signature within the N-terminal VHS domain of Gga2p resembling a motif found in other clathrin interacting proteins. These data provide an explanation for the TGN-specific membrane recruitment of Gga2p.