Phosphatidylinositol 4-phosphate formation at ER exit sites regulates ER export.
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.
Blumental-Perry
Anna
A
Department of Cell Biology, University of Pittsburgh School of Medicine, 3500 Terrace Street, Pittsburgh, Pennsylvania 15261, USA.
Haney
Charles J
CJ
Weixel
Kelly M
KM
Watkins
Simon C
SC
Weisz
Ora A
OA
Aridor
Meir
M
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*
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