The clathrin adaptor Gga2p is a phosphatidylinositol 4-phosphate effector at the Golgi exit.
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.
Demmel
Lars
L
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, D-01307, Germany.
Gravert
Maike
M
Ercan
Ebru
E
Habermann
Bianca
B
Müller-Reichert
Thomas
T
Kukhtina
Viktoria
V
Haucke
Volker
V
Baust
Thorsten
T
Sohrmann
Marc
M
Kalaidzidis
Yannis
Y
Klose
Christian
C
Beck
Mike
M
Peter
Matthias
M
Walch-Solimena
Christiane
C
D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism; D020727:ADP-Ribosylation Factors / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D002966:Clathrin / Q000378:metabolism*; D016681:Genome, Fungal / Q000235:genetics; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism / Q000648:ultrastructure
D033942:Adaptor Proteins, Vesicular Transport; D002966:Clathrin; C497361:Gga2 protein, S cerevisiae; D018129:Phosphatidylinositol Phosphates; D029701:Saccharomyces cerevisiae Proteins; C037178:phosphatidylinositol 4-phosphate; D019870:1-Phosphatidylinositol 4-Kinase; C441760:PIK1 protein, S cerevisiae; D020727:ADP-Ribosylation Factors