Phosphatidylinositol 4 Phosphate Regulates Targeting of Clathrin Adaptor AP-1 Complexes to the Golgi

• Published in: Cell Vol. 114; no. 3; pp. 299 - 310
• Main Authors: Wang, Ying Jie, Wang, Jing, Sun, Hui Qiao, Martinez, Manuel, Sun, Yu Xiao, Macia, Eric, Kirchhausen, Tomas, Albanesi, Joseph P., Roth, Michael G., Yin, Helen L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08-08-2003
• Subjects: Adaptor Protein Complex 1 - metabolism; Animals; Biomarkers; Cell Membrane - metabolism; Clathrin - metabolism; COS Cells; 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; Recombinant Fusion Proteins - metabolism; RNA Interference
• ISSN: 0092-8674; 1097-4172
• 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 PI4KIIα, a Golgi resident phosphatidylinositol 4 kinase, to determine whether PI(4)P directly regulates the Golgi. PI4KIIα 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 PI4KIIα 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.