Endoplasmic reticulum (ER)-to-Golgi trafficking is a central process of the secretory system of eukaryotic cells that ensures proper spatiotemporal sorting of proteins and lipids. However, the nature of the ER-Golgi intermediate compartments (ERGICs) and the molecular mechanisms mediating the transition between ERGICs and the Golgi, as well as the universality of these processes among eukaryotes, remain undiscovered. Here we identify a reticulated tubulo-vesicular network, labelled by MEMBRIN proteins, that is mostly independent of the Golgi, highly dynamic at the ER-Golgi interface and crossed by ER-induced released luminal cargos. We find that plant ERGICs become stabilized by the interaction they establish with pre-existing Golgi and gradually mature into Golgi cisternae, this process being dependent on C24-ceramide sphingolipids. Our study is a major twist in the understanding of the Golgi, as it identifies that the ERGICs in plants comprise a Golgi-independent and highly dynamic tubular network from which arise more stable Golgi-associated pre-cisternae structures.
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http://dx.doi.org/10.1038/s41556-025-01624-x | DOI Listing |
Nat Cell Biol
February 2025
Laboratoire de Biogenèse Membranaire, Université de Bordeaux, CNRS UMR5200, Villenave d'Ornon, France.
Endoplasmic reticulum (ER)-to-Golgi trafficking is a central process of the secretory system of eukaryotic cells that ensures proper spatiotemporal sorting of proteins and lipids. However, the nature of the ER-Golgi intermediate compartments (ERGICs) and the molecular mechanisms mediating the transition between ERGICs and the Golgi, as well as the universality of these processes among eukaryotes, remain undiscovered. Here we identify a reticulated tubulo-vesicular network, labelled by MEMBRIN proteins, that is mostly independent of the Golgi, highly dynamic at the ER-Golgi interface and crossed by ER-induced released luminal cargos.
View Article and Find Full Text PDFUnlabelled: Within cellular membranes, sphingomyelin is associated with cholesterol and this complex facilitates homeostatic regulation of membrane viscosity. Acute cholesterol depletion increases the synthesis of very-long-chain (VLC) sphingomyelin, but a link between lipid sensing and sphingolipid synthesis is lacking. Using sphingolipid metabolic flux analysis, we observed that VLC-ceramide, the precursor to VLC complex sphingolipids that are produced in the Golgi apparatus, was rapidly consumed after cholesterol depletion, while synthesis of long-chain sphingolipids was unaffected.
View Article and Find Full Text PDFDev Cell
February 2025
Department of Pharmacology, Woo Choo Lee Institute for Precision Drug Development, Graduate School of Medical Science Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. Electronic address:
Cellular stresses, particularly endoplasmic reticulum (ER) stress induced by ER-to-Golgi transport blockade, trigger Golgi-independent secretion of cytosolic and transmembrane proteins. However, the molecular mechanisms underlying this unconventional protein secretion (UPS) remain largely elusive. Here, we report that an ER tubulovesicular structure (ER tubular body [ER-TB]), shaped by the tubular ER-phagy receptors ATL3 and RTN3L, plays an important role in stress-induced UPS of transmembrane proteins such as cystic fibrosis transmembrane conductance regulator (CFTR) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein.
View Article and Find Full Text PDFNat Commun
January 2025
Life Sciences Institute, Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
The heterodimeric Rab3GAP complex is a guanine nucleotide exchange factor (GEF) for the Rab18 GTPase that regulates lipid droplet metabolism, ER-to-Golgi trafficking, secretion, and autophagy. Why both subunits of Rab3GAP are required for Rab18 GEF activity and the molecular basis of how Rab3GAP engages and activates its cognate substrate are unknown. Here we show that human Rab3GAP is conformationally flexible and potentially autoinhibited by the C-terminal domain of its Rab3GAP2 subunit.
View Article and Find Full Text PDFBiol Pharm Bull
January 2025
Faculty of Pharmacy and Pharmaceutical Sciences, Josai University.
Ceramide (Cer) is synthesized in the endoplasmic reticulum (ER) using sphinganine as the common backbone and is then transported to the Golgi apparatus to synthesize two complex sphingolipids, sphingomyelin (SM) and glucosylceramide (GlcCer). Brefeldin A (BFA) affects the structure of the Golgi apparatus, resulting in the redistribution of the Golgi proteins into the ER. Therefore, BFA has been used to examine the ER-to-Golgi trafficking of lipids, but the detailed lipid changes in cells upon BFA treatment are not fully understood.
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