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

Proc Natl Acad Sci U S A. 2017 Mar 28;114(13):3433-3438. doi: 10.1073/pnas.1615163114. Epub 2017 Mar 13.


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.

Keywords: Gga adaptors; clathrin; phosphatidylinositol 4-kinase; phosphatidylinositol 4-phosphate; trans-Golgi network.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Phosphatidylinositol 4-Kinase / chemistry
  • 1-Phosphatidylinositol 4-Kinase / genetics
  • 1-Phosphatidylinositol 4-Kinase / metabolism*
  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism
  • Adaptor Proteins, Vesicular Transport / chemistry
  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Amino Acid Motifs
  • Clathrin-Coated Vesicles / metabolism
  • HeLa Cells
  • Humans
  • Phosphotransferases (Alcohol Group Acceptor) / chemistry
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Binding
  • Protein Domains
  • Protein Transport
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • trans-Golgi Network / genetics
  • trans-Golgi Network / metabolism*


  • Adaptor Proteins, Vesicular Transport
  • GGA2 protein, human
  • Gga2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Phosphotransferases (Alcohol Group Acceptor)
  • 1-Phosphatidylinositol 4-Kinase
  • PIK1 protein, S cerevisiae
  • phosphatidylinositol 4-kinase IIIbeta, human
  • ADP-Ribosylation Factors