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Journal of Molecular Cell Biology Feb 2023Surfeit 4 is a polytopic transmembrane protein that primarily resides in the endoplasmic reticulum (ER) membrane. It is ubiquitously expressed and functions as a cargo... (Review)
Review
Surfeit 4 is a polytopic transmembrane protein that primarily resides in the endoplasmic reticulum (ER) membrane. It is ubiquitously expressed and functions as a cargo receptor, mediating cargo transport from the ER to the Golgi apparatus via the canonical coat protein complex II (COPII)-coated vesicles or specific vesicles. It also participates in ER-Golgi protein trafficking through a tubular network. Meanwhile, it facilitates retrograde transportation of cargos from the Golgi apparatus to the ER through COPI-coated vesicles. Surf4 can selectively mediate export of diverse cargos, such as PCSK9 very low-density lipoprotein (VLDL), progranulin, α1-antitrypsin, STING, proinsulin, and erythropoietin. It has been implicated in facilitating VLDL secretion, promoting cell proliferation and migration, and increasing replication of positive-strand RNA viruses. Therefore, Surf4 plays a crucial role in various physiological and pathophysiological processes and emerges as a promising therapeutic target. However, the molecular mechanisms by which Surf4 selectively sorts diverse cargos for ER-Golgi protein trafficking remain elusive. Here, we summarize the most recent advances in Surf4, focusing on its role in lipid metabolism.
Topics: Humans; Golgi Apparatus; Lipid Metabolism; Membrane Proteins; Proprotein Convertase 9; Protein Transport
PubMed: 36574593
DOI: 10.1093/jmcb/mjac063 -
Trends in Biochemical Sciences Dec 2020It has been demonstrated that two Golgi stacking proteins, GRASP55 and GRASP65, self-interact to form trans-oligomers that tether adjacent Golgi membranes into stacks... (Review)
Review
It has been demonstrated that two Golgi stacking proteins, GRASP55 and GRASP65, self-interact to form trans-oligomers that tether adjacent Golgi membranes into stacks and ribbons in mammalian cells. This ensures proper functioning of the Golgi apparatus in protein trafficking and processing. More recently, GRASP proteins have drawn extensive attention from researchers due to their diverse and essential roles in and out of the Golgi in different organisms. In this review, we summarize their established roles in Golgi structure formation and function under physiological conditions. We then highlight the emerging and divergent roles for individual GRASP proteins, focusing on GRASP65 in cell migration and apoptosis and GRASP55 in unconventional protein secretion and autophagy under stress or pathological conditions.
Topics: Animals; Cell Movement; Golgi Apparatus; Golgi Matrix Proteins; Protein Transport
PubMed: 32893104
DOI: 10.1016/j.tibs.2020.08.001 -
FEBS Letters Nov 2022Formation of disulfide bonds in secreted and cell-surface proteins involves numerous enzymes and chaperones abundant in the endoplasmic reticulum (ER), the first and... (Review)
Review
Formation of disulfide bonds in secreted and cell-surface proteins involves numerous enzymes and chaperones abundant in the endoplasmic reticulum (ER), the first and main site for disulfide bonding in the secretory pathway. Although the Golgi apparatus is the major station after the ER, little is known about thiol-based redox activity in this compartment. QSOX1 and its paralog QSOX2 are the only known Golgi-resident enzymes catalyzing disulfide bonding. The localization of disulfide catalysts in an organelle downstream of the ER in the secretory pathway has long been puzzling. Recently, it has emerged that QSOX1 regulates particular glycosyltransferases, thereby influencing a central activity of the Golgi. Surprisingly, a few important disulfide-mediated multimerization events occurring in the Golgi were found to be independent of QSOX1. These multimerization events depend, however, on the low pH of the Golgi lumen and secretory granules. We compare and contrast disulfide-mediated multimerization in the ER vs. the Golgi to illustrate the variety of mechanisms controlling covalent supramolecular assembly of secreted proteins.
Topics: Golgi Apparatus; Endoplasmic Reticulum; Proteins; Oxidation-Reduction; Disulfides
PubMed: 36214053
DOI: 10.1002/1873-3468.14510 -
Cell Reports Jun 2023The regulation of antiviral immunity is crucial in maintaining host immune homeostasis, a process that involves dynamic modulations of host organelles. The Golgi...
The regulation of antiviral immunity is crucial in maintaining host immune homeostasis, a process that involves dynamic modulations of host organelles. The Golgi apparatus is increasingly perceived as a host organelle functioning as a critical platform for innate immunity, but the detailed mechanism by which it regulates antiviral immunity remains elusive. Here, we identify the Golgi-localized G protein-coupled receptor 108 (GPR108) as a regulator of type Ι interferon responses by targeting interferon regulatory factor 3 (IRF3). Mechanistically, GPR108 enhances the ubiquitin ligase Smad ubiquitylation regulatory factor 1 (Smurf1)-mediated K63-linked polyubiquitination of phosphorylated IRF3 for nuclear dot 10 protein 52 (NDP52)-dependent autophagic degradation, leading to suppression of antiviral immune responses against DNA or RNA viruses. Taken together, our study provides insight into the crosstalk between the Golgi apparatus and antiviral immunity via a dynamic and spatiotemporal regulation of GPR108-Smurf1 axis, thereby indicating a potential target for treating viral infection.
Topics: Antiviral Agents; Golgi Apparatus; Immunity, Innate; Ubiquitin-Protein Ligases; Ubiquitination; Receptors, G-Protein-Coupled
PubMed: 37330913
DOI: 10.1016/j.celrep.2023.112655 -
Methods in Cell Biology 2021
Topics: Endoplasmic Reticulum; Golgi Apparatus; Intracellular Membranes; Protein Transport
PubMed: 34311874
DOI: 10.1016/S0091-679X(21)00081-9 -
The Plant Cell Jan 2022Endomembrane trafficking is essential for all eukaryotic cells. The best-characterized membrane trafficking organelles include the endoplasmic reticulum (ER), Golgi... (Review)
Review
Endomembrane trafficking is essential for all eukaryotic cells. The best-characterized membrane trafficking organelles include the endoplasmic reticulum (ER), Golgi apparatus, early and recycling endosomes, multivesicular body, or late endosome, lysosome/vacuole, and plasma membrane. Although historically plants have given rise to cell biology, our understanding of membrane trafficking has mainly been shaped by the much more studied mammalian and yeast models. Whereas organelles and major protein families that regulate endomembrane trafficking are largely conserved across all eukaryotes, exciting variations are emerging from advances in plant cell biology research. In this review, we summarize the current state of knowledge on plant endomembrane trafficking, with a focus on four distinct trafficking pathways: ER-to-Golgi transport, endocytosis, trans-Golgi network-to-vacuole transport, and autophagy. We acknowledge the conservation and commonalities in the trafficking machinery across species, with emphasis on diversity and plant-specific features. Understanding the function of organelles and the trafficking machinery currently nonexistent in well-known model organisms will provide great opportunities to acquire new insights into the fundamental cellular process of membrane trafficking.
Topics: Autophagy; Biological Transport; Endocytosis; Endoplasmic Reticulum; Golgi Apparatus; Plant Physiological Phenomena; Vacuoles
PubMed: 34550393
DOI: 10.1093/plcell/koab235 -
Nature Communications Jan 2021Coat protein complex I (COP-I) mediates the retrograde transport from the Golgi apparatus to the endoplasmic reticulum (ER). Mutation of the COPA gene, encoding one of...
Coat protein complex I (COP-I) mediates the retrograde transport from the Golgi apparatus to the endoplasmic reticulum (ER). Mutation of the COPA gene, encoding one of the COP-I subunits (α-COP), causes an immune dysregulatory disease known as COPA syndrome. The molecular mechanism by which the impaired retrograde transport results in autoinflammation remains poorly understood. Here we report that STING, an innate immunity protein, is a cargo of the retrograde membrane transport. In the presence of the disease-causative α-COP variants, STING cannot be retrieved back to the ER from the Golgi. The forced Golgi residency of STING results in the cGAS-independent and palmitoylation-dependent activation of the STING downstream signaling pathway. Surf4, a protein that circulates between the ER/ ER-Golgi intermediate compartment/ Golgi, binds STING and α-COP, and mediates the retrograde transport of STING to the ER. The STING/Surf4/α-COP complex is disrupted in the presence of the disease-causative α-COP variant. We also find that the STING ligand cGAMP impairs the formation of the STING/Surf4/α-COP complex. Our results suggest a homeostatic regulation of STING at the resting state by retrograde membrane traffic and provide insights into the pathogenesis of COPA syndrome.
Topics: Animals; Brefeldin A; COP-Coated Vesicles; Cell Membrane; Endoplasmic Reticulum; Fibroblasts; Golgi Apparatus; HEK293 Cells; Homeostasis; Humans; Lipoylation; Luciferases; Membrane Proteins; Mice; Nucleotidyltransferases; Protein Binding; Protein Transport
PubMed: 33397928
DOI: 10.1038/s41467-020-20234-9 -
Trends in Cell Biology Dec 2023Mechanobiology studies the mechanisms by which cells sense and respond to physical forces, and the role of these forces in shaping cells and tissues themselves.... (Review)
Review
Mechanobiology studies the mechanisms by which cells sense and respond to physical forces, and the role of these forces in shaping cells and tissues themselves. Mechanosensing can occur at the plasma membrane, which is directly exposed to external forces, but also in the cell's interior, for example, through deformation of the nucleus. Less is known on how the function and morphology of organelles are influenced by alterations in their own mechanical properties, or by external forces. Here, we discuss recent advances on the mechanosensing and mechanotransduction of organelles, including the endoplasmic reticulum (ER), the Golgi apparatus, the endo-lysosmal system, and the mitochondria. We highlight open questions that need to be addressed to gain a broader understanding of the role of organelle mechanobiology.
Topics: Humans; Mechanotransduction, Cellular; Organelles; Golgi Apparatus; Endoplasmic Reticulum; Mitochondria; Cell Membrane
PubMed: 37236902
DOI: 10.1016/j.tcb.2023.05.001 -
The New Phytologist Jun 2023Manganese (Mn) is pivotal for plant growth and development but little is known about the processes that control its homeostasis in the cell. A spotlight on the pools of... (Review)
Review
Manganese (Mn) is pivotal for plant growth and development but little is known about the processes that control its homeostasis in the cell. A spotlight on the pools of intracellular manganese and their cellular function has recently been gained through the characterization of new Mn transporters. In particular, transporters catalyzing the ins and outs of Mn at the various Golgi membranes have revealed the central role of the Golgi pool of Mn in the synthesis of the cell wall and as a reservoir for the numerous cellular Mn-dependent pathways whose calibration relies on a set of Golgi-resident transporters of the BICAT and NRAMP families.
Topics: Manganese; Golgi Apparatus; Homeostasis; Membrane Transport Proteins
PubMed: 36856330
DOI: 10.1111/nph.18846 -
Journal of Cerebral Blood Flow and... Apr 2023Glycosylation of lipids and proteins significantly increases the molecular diversity in the brain. Membrane-localized glycoconjugates facilitate critical neuro-immune... (Review)
Review
Glycosylation of lipids and proteins significantly increases the molecular diversity in the brain. Membrane-localized glycoconjugates facilitate critical neuro-immune interactions. Therefore, glycodysregulation is increasingly recognized as a novel hallmark of various acute and chronic neurological diseases. Although RNAs are heavily modified, they are never thought to be substrates for glycosylation due to their inaccessibility to the glycosylation machinery in the Golgi apparatus. The astonishing discovery of cell surface glycoRNAs opened new avenues for glycomedicine. This review highlighted the key features of GlycoRNAs and further discussed their potential immunomodulatory role in the brain, particularly focusing on post-stroke neuroinflammation.
Topics: Glycosylation; Golgi Apparatus; Cell Membrane; Brain
PubMed: 36644904
DOI: 10.1177/0271678X231151995