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

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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

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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