Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi

Cell. 2003 Aug 8;114(3):299-310. doi: 10.1016/s0092-8674(03)00603-2.


Phosphatidylinositol 4 phosphate [PI(4)P] is essential for secretion in yeast, but its role in mammalian cells is unclear. Current paradigms propose that PI(4)P acts primarily as a precursor to phosphatidylinositol 4,5 bisphosphate (PIP2), an important plasma membrane regulator. We found that PI(4)P is enriched in the mammalian Golgi, and used RNA interference (RNAi) of PI4KIIalpha, a Golgi resident phosphatidylinositol 4 kinase, to determine whether PI(4)P directly regulates the Golgi. PI4KIIalpha RNAi decreases Golgi PI(4)P, blocks the recruitment of clathrin adaptor AP-1 complexes to the Golgi, and inhibits AP-1-dependent functions. This AP-1 binding defect is rescued by adding back PI(4)P. In addition, purified AP-1 binds PI(4)P, and anti-PI(4)P inhibits the in vitro recruitment of cytosolic AP-1 to normal cellular membranes. We propose that PI4KIIalpha establishes the Golgi's unique lipid-defined organelle identity by generating PI(4)P-rich domains that specify the docking of the AP-1 coat machinery.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Protein Complex 1 / metabolism*
  • Animals
  • Biomarkers
  • COS Cells
  • Cell Membrane / metabolism
  • Clathrin / metabolism*
  • Exocytosis / physiology
  • Golgi Apparatus / metabolism*
  • HeLa Cells
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Phosphatidylinositol Phosphates / metabolism*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Binding
  • Protein Transport / physiology
  • RNA Interference
  • Recombinant Fusion Proteins / metabolism


  • Adaptor Protein Complex 1
  • Biomarkers
  • Clathrin
  • Isoenzymes
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates
  • Recombinant Fusion Proteins
  • phosphatidylinositol 4-phosphate
  • Phosphotransferases (Alcohol Group Acceptor)
  • 1-phosphatidylinositol-4-phosphate 5-kinase