title: COPII coat composition is actively regulated by luminal cargo maturation.
abstract: BACKGROUND
  Export from the ER is an essential process driven by the COPII coat, which forms vesicles at ER exit sites (ERESs) to transport mature secretory proteins to the Golgi. Although the basic mechanism of COPII assembly is known, how COPII machinery is regulated to meet varying cellular secretory demands is unclear.
  
  
  RESULTS
  Here, we report a specialized COPII system that is actively recruited by luminal cargo maturation. Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are luminal secretory proteins anchored to the membrane by the glycolipid GPI. After protein attachment in the ER lumen, lipid and glycan parts of the GPI anchor are remodeled. In yeast, GPI-lipid remodeling concentrates GPI-APs into specific ERESs. We found that GPI-glycan remodeling induces subsequent recruitment of the specialized ER export machinery that enables vesicle formation from these specific ERESs. First, the transmembrane cargo receptor p24 complex binds GPI-APs as a lectin by recognizing the remodeled GPI-glycan. Binding of remodeled cargo induces the p24 complex to recruit the COPII subtype Lst1p, specifically required for GPI-AP ER export.
  
  
  CONCLUSIONS
  Our results show that COPII coat recruitment by cargo receptors is not constitutive but instead is actively regulated by binding of mature ligands. Therefore, we reveal a novel functional link between luminal cargo maturation and COPII vesicle budding, providing a mechanism to adjust specialized COPII vesicle production to the amount and quality of their luminal cargos that are ready for ER exit. This helps to understand how the ER export machinery adapts to different needs for luminal cargo secretion.
authors.affiliation: Department of Cell Biology, University of Seville, 41012 Seville, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Manzano-Lopez
authors.affiliation: Department of Cell Biology, University of Seville, 41012 Seville, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Perez-Linero
authors.affiliation: Department of Cell Biology, University of Seville, 41012 Seville, Spain.
authors.forename: Auxiliadora
authors.initials: A
authors.lastname: Aguilera-Romero
authors.affiliation: Department of Cell Biology, University of Seville, 41012 Seville, Spain.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Martin
authors.affiliation: Department of Bioresource Science and Technology, Hiroshima University, Hiroshima 739-8528, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Okano
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany.
authors.forename: Daniel Varon
authors.initials: DV
authors.lastname: Silva
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeberger
authors.affiliation: NCCR Chemical Biology and Department of Biochemistry, Sciences II, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Howard
authors.initials: H
authors.lastname: Riezman
authors.affiliation: Department of Bioresource Science and Technology, Hiroshima University, Hiroshima 739-8528, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Funato
authors.affiliation: Department of Genetics, University of Seville, 41012 Seville, Spain.
authors.forename: Veit
authors.initials: V
authors.lastname: Goder
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), 41092 Seville, Spain.
authors.forename: Ralf E
authors.initials: RE
authors.lastname: Wellinger
authors.affiliation: Department of Cell Biology, University of Seville, 41012 Seville, Spain. Electronic address: mmuniz@us.es.
authors.forename: Manuel
authors.initials: M
authors.lastname: Muñiz
mesh_terms: D022181:COP-Coated Vesicles / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
chemical_list: D017261:Glycosylphosphatidylinositols