Phosphatidylinositol 4-phosphate formation at ER exit sites regulates ER export

Dev Cell. 2006 Nov;11(5):671-82. doi: 10.1016/j.devcel.2006.09.001.


The mechanisms that regulate endoplasmic reticulum (ER) exit-site (ERES) assembly and COPII-mediated ER export are currently unknown. We analyzed the role of phosphatidylinositols (PtdIns) in regulating ER export. Utilizing pleckstrin homology domains and a PtdIns phosphatase to specifically sequester or reduce phosphorylated PtdIns levels, we found that PtdIns 4-phosphate (PtsIns4P) is required to promote COPII-mediated ER export. Biochemical and morphological in vitro analysis revealed dynamic and localized PtsIns4P formation at ERES. PtdIns4P was utilized to support Sar1-induced proliferation and constriction of ERES membranes. PtdIns4P also assisted in Sar1-induced COPII nucleation at ERES. Therefore, localized dynamic remodeling of PtdIns marks ERES membranes to regulate COPII-mediated ER export.

Publication types

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

MeSH terms

  • Animals
  • Biological Transport
  • COP-Coated Vesicles / physiology*
  • Cell Line
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum / ultrastructure
  • Intracellular Membranes / metabolism
  • Intracellular Membranes / ultrastructure
  • Membrane Proteins / physiology
  • Monomeric GTP-Binding Proteins / physiology
  • Phosphatidylinositol Phosphates / biosynthesis*
  • Phosphorylation
  • Rats
  • Vesicular Transport Proteins / physiology*


  • Membrane Proteins
  • Phosphatidylinositol Phosphates
  • Sac1 protein, mammalian
  • Vesicular Transport Proteins
  • phosphatidylinositol 4-phosphate
  • SAR1 protein, rat
  • Monomeric GTP-Binding Proteins