Rodriguez-Gallardo, SofiaKurokawa, KazuoSabido-Bozo, SusanaCortes-Gomez, AlejandroIkeda, AtsukoZoni, ValeriaAguilera-Romero, AuxiliadoraPerez-Linero, Ana MariaLopez, SergioWaga, MihoAraki, MisakoNakano, MiyakoRiezman, HowardFunato, KouichiVanni, StefanoNakano, AkihikoMuñiz, Manuel2022-04-212022-04-212020-12-11Rodriguez-Gallardo S, Kurokawa K, Sabido-Bozo S, Cortes-Gomez A, Ikeda A, Zoni V, et al. Ceramide chain length-dependent protein sorting into selective endoplasmic reticulum exit sites. Sci Adv. 2020 Dec 11;6(50):eaba8237http://hdl.handle.net/10668/3553Protein sorting in the secretory pathway is crucial to maintain cellular compartmentalization and homeostasis. In addition to coat-mediated sorting, the role of lipids in driving protein sorting during secretory transport is a longstanding fundamental question that still remains unanswered. Here, we conduct 3D simultaneous multicolor high-resolution live imaging to demonstrate in vivo that newly synthesized glycosylphosphatidylinositol-anchored proteins having a very long chain ceramide lipid moiety are clustered and sorted into specialized endoplasmic reticulum exit sites that are distinct from those used by transmembrane proteins. Furthermore, we show that the chain length of ceramide in the endoplasmic reticulum membrane is critical for this sorting selectivity. Our study provides the first direct in vivo evidence for lipid chain length-based protein cargo sorting into selective export sites of the secretory pathway.enAtribución-NoComercial 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc/4.0/CeramidesGlycosylphosphatidylinositolEndoplasmic reticulumLipidsMembranesProteinsReticulumSecretory pathwayCeramidasRetículo endoplásmicoLípidosProteínasReticulumVías secretoriasMembranasGlicosilfosfatidilinositolesMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Biological Transport::Protein TransportMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::CeramidesMedical Subject Headings::Chemicals and Drugs::Lipids::Glycolipids::GlycosylphosphatidylinositolsMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Endoplasmic ReticulumMedical Subject Headings::Chemicals and Drugs::LipidsMedical Subject Headings::Anatomy::Tissues::MembranesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::ProteinsMedical Subject Headings::Anatomy::Animal Structures::Stomach, Ruminant::ReticulumMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Biological Transport::Secretory PathwayMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Homeostasisresearch article33310842open access10.1126/sciadv.aba82372375-2548PMC7732199