Javier Manzano-Lopez1, Ana M Perez-Linero1, Auxiliadora Aguilera-Romero1, Maria E Martin1, Tatsuki Okano2, Daniel Varon Silva3, Peter H Seeberger3, Howard Riezman4, Kouichi Funato2, Veit Goder5, Ralf E Wellinger6, Manuel Muñiz7. 1. Department of Cell Biology, University of Seville, 41012 Seville, Spain. 2. Department of Bioresource Science and Technology, Hiroshima University, Hiroshima 739-8528, Japan. 3. Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany. 4. NCCR Chemical Biology and Department of Biochemistry, Sciences II, University of Geneva, 1211 Geneva 4, Switzerland. 5. Department of Genetics, University of Seville, 41012 Seville, Spain. 6. Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), 41092 Seville, Spain. 7. Department of Cell Biology, University of Seville, 41012 Seville, Spain. Electronic address: mmuniz@us.es.
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.
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: Noelia Pastor-Cantizano; Juan Carlos Montesinos; César Bernat-Silvestre; María Jesús Marcote; Fernando Aniento Journal: Protoplasma Date: 2015-07-30 Impact factor: 3.356
Authors: Jennifer G D'Arcangelo; Jonathan Crissman; Silvere Pagant; Alenka Čopič; Catherine F Latham; Erik L Snapp; Elizabeth A Miller Journal: Curr Biol Date: 2015-04-30 Impact factor: 10.834