title: Phosphatidylinositol 4-phosphate formation at ER exit sites regulates ER export.
abstract: 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.
authors.affiliation: Department of Cell Biology, University of Pittsburgh School of Medicine, 3500 Terrace Street, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Blumental-Perry
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Haney
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Weixel
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
authors.forename: Ora A
authors.initials: OA
authors.lastname: Weisz
authors.forename: Meir
authors.initials: M
authors.lastname: Aridor
mesh_terms: D000818:Animals; D001692:Biological Transport; D022181:COP-Coated Vesicles / Q000502:physiology*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D007425:Intracellular Membranes / Q000378:metabolism / Q000648:ultrastructure; D008565:Membrane Proteins / Q000502:physiology; D020559:Monomeric GTP-Binding Proteins / Q000502:physiology; D018129:Phosphatidylinositol Phosphates / Q000096:biosynthesis*; D010766:Phosphorylation; D051381:Rats; D033921:Vesicular Transport Proteins / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; D018129:Phosphatidylinositol Phosphates; C416669:Sac1 protein, mammalian; D033921:Vesicular Transport Proteins; C037178:phosphatidylinositol 4-phosphate; C487879:SAR1 protein, rat; D020559:Monomeric GTP-Binding Proteins