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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 -
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 -
Cells Jul 2023The Golgi apparatus plays a central role in protein sorting, modification and trafficking within cells; its dysregulation has been implicated in various cancers... (Review)
Review
The Golgi apparatus plays a central role in protein sorting, modification and trafficking within cells; its dysregulation has been implicated in various cancers including those affecting the GI tract. This review highlights two Golgi target proteins, namely GOLPH3 and GOLGA proteins, from this apparatus as they relate to gastroenterological cancers. GOLPH3-a highly conserved protein of the trans-Golgi network-has become a key player in cancer biology. Abnormal expression of GOLPH3 has been detected in various gastrointestinal cancers including gastric, colorectal and pancreatic cancers. GOLPH3 promotes tumor cell proliferation, survival, migration and invasion via various mechanisms including activating the PI3K/Akt/mTOR signaling pathway as well as altering Golgi morphology and vesicular trafficking. GOLGA family proteins such as GOLGA1 (golgin-97) and GOLGA7 (golgin-84) have also been implicated in gastroenterological cancers. GOLGA1 plays an essential role in protein trafficking within the Golgi apparatus and has been associated with poor patient survival rates and increased invasiveness; GOLGA7 maintains Golgi structure while having been shown to affect protein glycosylation processes. GOLPH3 and GOLGA proteins play a pivotal role in gastroenterological cancer, helping researchers unlock molecular mechanisms and identify therapeutic targets. Their dysregulation affects various cellular processes including signal transduction, vesicular trafficking and protein glycosylation, all contributing to tumor aggressiveness and progression.
Topics: Humans; Phosphatidylinositol 3-Kinases; Membrane Proteins; Neoplasms; Golgi Apparatus; Gastrointestinal Tract
PubMed: 37508488
DOI: 10.3390/cells12141823 -
Philosophical Transactions of the Royal... Sep 2014A shared feature among all microtubule (MT)-dependent processes is the requirement for MTs to be organized in arrays of defined geometry. At a fundamental level, this is... (Review)
Review
A shared feature among all microtubule (MT)-dependent processes is the requirement for MTs to be organized in arrays of defined geometry. At a fundamental level, this is achieved by precisely controlling the timing and localization of the nucleation events that give rise to new MTs. To this end, MT nucleation is restricted to specific subcellular sites called MT-organizing centres. The primary MT-organizing centre in proliferating animal cells is the centrosome. However, the discovery of MT nucleation capacity of the Golgi apparatus (GA) has substantially changed our understanding of MT network organization in interphase cells. Interestingly, MT nucleation at the Golgi apparently relies on multiprotein complexes, similar to those present at the centrosome, that assemble at the cis-face of the organelle. In this process, AKAP450 plays a central role, acting as a scaffold to recruit other centrosomal proteins important for MT generation. MT arrays derived from either the centrosome or the GA differ in their geometry, probably reflecting their different, yet complementary, functions. Here, I review our current understanding of the molecular mechanisms involved in MT nucleation at the GA and how Golgi- and centrosome-based MT arrays work in concert to ensure the formation of a pericentrosomal polarized continuous Golgi ribbon structure, a critical feature for cell polarity in mammalian cells. In addition, I comment on the important role of the Golgi-nucleated MTs in organizing specialized MT arrays that serve specific functions in terminally differentiated cells.
Topics: A Kinase Anchor Proteins; Centrosome; Cytoskeletal Proteins; Golgi Apparatus; Microtubules; Mitosis; Models, Biological
PubMed: 25047616
DOI: 10.1098/rstb.2013.0462 -
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 -
Handbook of Experimental Pharmacology 2018The conserved oligomeric Golgi (COG) complex is an evolutionary conserved multi-subunit vesicle tethering complex essential for the majority of Golgi apparatus... (Review)
Review
The conserved oligomeric Golgi (COG) complex is an evolutionary conserved multi-subunit vesicle tethering complex essential for the majority of Golgi apparatus functions: protein and lipid glycosylation and protein sorting. COG is present in neuronal cells, but the repertoire of COG function in different Golgi-like compartments is an enigma. Defects in COG subunits cause alteration of Golgi morphology, protein trafficking, and glycosylation resulting in human congenital disorders of glycosylation (CDG) type II. In this review we summarize and critically analyze recent advances in the function of Golgi and Golgi-like compartments in neuronal cells and functions and dysfunctions of the COG complex and its partner proteins.
Topics: Adaptor Proteins, Vesicular Transport; Animals; Glycosylation; Golgi Apparatus; Humans; Neurons; Protein Transport
PubMed: 29063274
DOI: 10.1007/164_2017_65 -
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 -
International Journal of Molecular... Apr 2021The Golgi apparatus is known to underpin many important cellular homeostatic functions, including trafficking, sorting and modifications of proteins or lipids. These... (Review)
Review
The Golgi apparatus is known to underpin many important cellular homeostatic functions, including trafficking, sorting and modifications of proteins or lipids. These functions are dysregulated in neurodegenerative diseases, cancer, infectious diseases and cardiovascular diseases, and the number of disease‑related genes associated with Golgi apparatus is on the increase. Recently, many studies have suggested that the mutations in the genes encoding Golgi resident proteins can trigger the occurrence of diseases. By summarizing the pathogenesis of these genetic diseases, it was found that most of these diseases have defects in membrane trafficking. Such defects typically result in mislocalization of proteins, impaired glycosylation of proteins, and the accumulation of undegraded proteins. In the present review, we aim to understand the patterns of mutations in the genes encoding Golgi resident proteins and decipher the interplay between Golgi resident proteins and membrane trafficking pathway in cells. Furthermore, the detection of Golgi resident protein in human serum samples has the potential to be used as a diagnostic tool for diseases, and its central role in membrane trafficking pathways provides possible targets for disease therapy. Thus, we also introduced the clinical value of Golgi apparatus in the present review.
Topics: Animals; Biomarkers; Disease; Golgi Apparatus; Humans; Intracellular Membranes; Mutation
PubMed: 33537825
DOI: 10.3892/ijmm.2021.4871 -
Biomolecules Aug 2015Proteoglycans (PGs) are glycosylated proteins of biological importance at cell surfaces, in the extracellular matrix, and in the circulation. PGs are produced and... (Review)
Review
Proteoglycans (PGs) are glycosylated proteins of biological importance at cell surfaces, in the extracellular matrix, and in the circulation. PGs are produced and modified by glycosaminoglycan (GAG) chains in the secretory pathway of animal cells. The most common GAG attachment site is a serine residue followed by a glycine (-ser-gly-), from which a linker tetrasaccharide extends and may continue as a heparan sulfate, a heparin, a chondroitin sulfate, or a dermatan sulfate GAG chain. Which type of GAG chain becomes attached to the linker tetrasaccharide is influenced by the structure of the protein core, modifications occurring to the linker tetrasaccharide itself, and the biochemical environment of the Golgi apparatus, where GAG polymerization and modification by sulfation and epimerization take place. The same cell type may produce different GAG chains that vary, depending on the extent of epimerization and sulfation. However, it is not known to what extent these differences are caused by compartmental segregation of protein cores en route through the secretory pathway or by differential recruitment of modifying enzymes during synthesis of different PGs. The topic of this review is how different aspects of protein structure, cellular biochemistry, and compartmentalization may influence GAG synthesis.
Topics: Animals; Glycosaminoglycans; Golgi Apparatus; Humans; Membrane Transport Proteins; Secretory Pathway
PubMed: 26308067
DOI: 10.3390/biom5032003