Conserved role for Gga proteins in phosphatidylinositol 4-kinase localization to the trans-Golgi network.

Phosphoinositides serve as key membrane determinants for assembly of clathrin coat proteins that drive formation of clathrin-coated vesicles. At the trans-Golgi network (TGN), phosphatidylinositol 4-phosphate (PtdIns4P) plays important roles in recruitment of two major clathrin adaptors, Gga (Golgi-localized, gamma-adaptin ear homology, Arf-binding) proteins and the AP-1 (assembly protein-1) complex. The ...
molecular mechanisms that mediate localization of phosphatidylinositol kinases responsible for synthesis of PtdIns4P at the TGN are not well characterized. We identify two motifs in the yeast phosphatidylinositol 4-kinase, Pik1, which are required for binding to the VHS domain of Gga2. Mutations in these motifs that inhibit Gga2-VHS binding resulted in reduced Pik1 localization and delayed accumulation of PtdIns4P and recruitment of AP-1 to the TGN. The Pik1 homolog in mammals, PI4KIIIβ, interacted preferentially with the VHS domain of GGA2 compared with VHS domains of GGA1 and GGA3. Depletion of GGA2, but not GGA1 or GGA3, specifically affected PI4KIIIβ localization. These results reveal a conserved role for Gga proteins in regulating phosphatidylinositol 4-kinase function at the TGN.
Mesh Terms:
1-Phosphatidylinositol 4-Kinase, ADP-Ribosylation Factors, Adaptor Proteins, Vesicular Transport, Amino Acid Motifs, Clathrin-Coated Vesicles, HeLa Cells, Humans, Phosphotransferases (Alcohol Group Acceptor), Protein Binding, Protein Domains, Protein Transport, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, trans-Golgi Network
Proc. Natl. Acad. Sci. U.S.A.
Date: Dec. 28, 2016
Download Curated Data For This Publication
209779
Switch View:
  • Interactions 5