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

Ying Jie Wang, Jing Wang, Hui Qiao Sun, Manuel Martinez, Yu Xiao Sun, Eric Macia, Tomas Kirchhausen, Joseph P. Albanesi, Michael G. Roth, Helen L. Yin

Research output: Contribution to journalArticlepeer-review

444 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)299-310
Number of pages12
JournalCell
Volume114
Issue number3
DOIs
StatePublished - Aug 8 2003

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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