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Cells Jan 2022The Golgi apparatus is a membrane organelle located in the center of the protein processing and trafficking pathway. It consists of sub-compartments with distinct... (Review)
Review
The Golgi apparatus is a membrane organelle located in the center of the protein processing and trafficking pathway. It consists of sub-compartments with distinct biochemical compositions and functions. Main functions of the Golgi, including membrane trafficking, protein glycosylation, and sorting, require a well-maintained stable microenvironment in the sub-compartments of the Golgi, along with metal ion homeostasis. Metal ions, such as Ca, Mn, Zn, and Cu, are important cofactors of many Golgi resident glycosylation enzymes. The homeostasis of metal ions in the secretory pathway, which is required for proper function and stress response of the Golgi, is tightly regulated and maintained by transporters. Mutations in the transporters cause human diseases. Here we provide a review specifically focusing on the transporters that maintain Golgi metal ion homeostasis under physiological conditions and their alterations in diseases.
Topics: Animals; Disease; Golgi Apparatus; Health; Homeostasis; Humans; Ions; Metals
PubMed: 35053405
DOI: 10.3390/cells11020289 -
Cells Feb 2022The Golgi apparatus is a central hub for cellular protein trafficking and signaling. Golgi structure and function is tightly coupled and undergoes dynamic changes in... (Review)
Review
The Golgi apparatus is a central hub for cellular protein trafficking and signaling. Golgi structure and function is tightly coupled and undergoes dynamic changes in health and disease. A crucial requirement for maintaining Golgi homeostasis is the ability of the Golgi to target aberrant, misfolded, or otherwise unwanted proteins to degradation. Recent studies have revealed that the Golgi apparatus may degrade such proteins through autophagy, retrograde trafficking to the ER for ER-associated degradation (ERAD), and locally, through Golgi apparatus-related degradation (GARD). Here, we review recent discoveries in these mechanisms, highlighting the role of the Golgi in maintaining cellular homeostasis.
Topics: Golgi Apparatus; Homeostasis; Membrane Proteins; Protein Transport; Proteolysis
PubMed: 35269404
DOI: 10.3390/cells11050780 -
Nature Communications Feb 2023Apicomplexan parasite growth and replication relies on nutrient acquisition from host cells, in which intracellular multiplication occurs, yet the mechanisms that...
Apicomplexan parasite growth and replication relies on nutrient acquisition from host cells, in which intracellular multiplication occurs, yet the mechanisms that underlie the nutrient salvage remain elusive. Numerous ultrastructural studies have documented a plasma membrane invagination with a dense neck, termed the micropore, on the surface of intracellular parasites. However, the function of this structure remains unknown. Here we validate the micropore as an essential organelle for endocytosis of nutrients from the host cell cytosol and Golgi in the model apicomplexan Toxoplasma gondii. Detailed analyses demonstrated that Kelch13 is localized at the dense neck of the organelle and functions as a protein hub at the micropore for endocytic uptake. Intriguingly, maximal activity of the micropore requires the ceramide de novo synthesis pathway in the parasite. Thus, this study provides insights into the machinery underlying acquisition of host cell-derived nutrients by apicomplexan parasites that are otherwise sequestered from host cell compartments.
Topics: Toxoplasma; Endocytosis; Golgi Apparatus; Biological Transport; Protozoan Proteins
PubMed: 36813769
DOI: 10.1038/s41467-023-36571-4 -
The Journal of Clinical Investigation Jan 2023Most proteins destined for the extracellular space or various intracellular compartments must traverse the intracellular secretory pathway. The first step is the... (Review)
Review
Most proteins destined for the extracellular space or various intracellular compartments must traverse the intracellular secretory pathway. The first step is the recruitment and transport of cargoes from the endoplasmic reticulum (ER) lumen to the Golgi apparatus by coat protein complex II (COPII), consisting of five core proteins. Additional ER transmembrane proteins that aid cargo recruitment are referred to as cargo receptors. Gene duplication events have resulted in multiple COPII paralogs present in the mammalian genome. Here, we review the functions of each COPII protein, human disorders associated with each paralog, and evidence for functional conservation between paralogs. We also provide a summary of current knowledge regarding two prototypical cargo receptors in mammals, LMAN1 and SURF4, and their roles in human health and disease.
Topics: Animals; Humans; Protein Transport; COP-Coated Vesicles; Biological Transport; Membrane Proteins; Endoplasmic Reticulum; Golgi Apparatus; Mammals
PubMed: 36594468
DOI: 10.1172/JCI163838 -
The FEBS Journal Nov 2022We previously discovered an autophagy-like proteolysis mechanism that uses the Golgi membrane, namely, Golgi membrane-associated degradation (GOMED). Morphologically,... (Review)
Review
We previously discovered an autophagy-like proteolysis mechanism that uses the Golgi membrane, namely, Golgi membrane-associated degradation (GOMED). Morphologically, GOMED resembles canonical autophagy, but the two mechanisms have different cellular functions, as they degrade different substrates and use different membrane sources. Furthermore, although the molecules involved partially overlap, the core molecules are completely different. GOMED preferentially degrades Golgi-trafficking proteins, including insulin granules in pancreatic β-cells and ceruloplasmin in neurons, and is involved in a wide variety of physiological events.
Topics: Golgi Apparatus; Autophagy-Related Protein-1 Homolog; Autophagy; Proteolysis; Insulin-Secreting Cells
PubMed: 34787961
DOI: 10.1111/febs.16281 -
FEBS Letters Sep 2019The conserved Ypt/Rab GTPases regulate the different steps of all intracellular trafficking pathways. Ypt/Rabs are activated by their specific nucleotide exchangers... (Review)
Review
The conserved Ypt/Rab GTPases regulate the different steps of all intracellular trafficking pathways. Ypt/Rabs are activated by their specific nucleotide exchangers termed GEFs, and when GTP bound, they recruit their downstream effectors, which mediate vesicular transport substeps. In the yeast exocytic pathway, Ypt1 and Ypt31/32 regulate traffic through the Golgi and the conserved modular TRAPP complex acts a GEF for both Ypt1 and Ypt31/32. However, the precise localization and function of these Ypts have been under debate, as is the identity of their corresponding GEFs. We have established that Ypt1 and Ypt31 reside on the two sides of the Golgi, early and late, respectively, and regulate Golgi cisternal progression. We and others have shown that whereas a single TRAPP complex, TRAPP II, activates Ypt31, three TRAPP complexes can activate Ypt1: TRAPPs I, III, and IV. We propose that TRAPP I and II activate Ypt1 and Ypt31, respectively, at the Golgi, whereas TRAPP III and IV activate Ypt1 in autophagy. Resolving these issues is important because both Rabs and TRAPPs are implicated in multiple human diseases, ranging from cancer to neurodegenerative diseases.
Topics: Animals; Golgi Apparatus; Guanine Nucleotide Exchange Factors; Humans; Protein Transport; Vesicular Transport Proteins; rab GTP-Binding Proteins
PubMed: 31400292
DOI: 10.1002/1873-3468.13574 -
FEBS Letters Sep 2022In eukaryotes, the endomembrane system allows for spatiotemporal compartmentation of complicated cellular processes. The plant endomembrane system consists of the... (Review)
Review
In eukaryotes, the endomembrane system allows for spatiotemporal compartmentation of complicated cellular processes. The plant endomembrane system consists of the endoplasmic reticulum, the Golgi apparatus, the trans-Golgi network, the multivesicular body and the vacuole. Anterograde traffic from the endoplasmic reticulum to the Golgi apparatus is mediated by coat protein complex II (COPII) vesicles. Autophagy, an evolutionarily conserved catabolic process that turns over cellular materials upon nutrient deprivation or in adverse environments, exploits double-membrane autophagosomes to recycle unwanted constituents in the lysosome/vacuole. Accumulating evidence reveals novel functions of plant COPII vesicles in autophagy and their regulation by abiotic stresses. Here, we summarize current knowledge about plant COPII vesicles in endomembrane trafficking and then highlight recent findings showing their distinct roles in modulating the autophagic flux and stress responses.
Topics: Autophagy; COP-Coated Vesicles; Endoplasmic Reticulum; Golgi Apparatus; Protein Transport
PubMed: 35486434
DOI: 10.1002/1873-3468.14362 -
Science Signaling Nov 2022The clathrin-associated adaptor protein complex AP-1 stops STING signaling at the Golgi.
The clathrin-associated adaptor protein complex AP-1 stops STING signaling at the Golgi.
Topics: Clathrin; Adaptor Protein Complex alpha Subunits; Adaptor Proteins, Vesicular Transport; Golgi Apparatus; Adaptor Protein Complex 1
PubMed: 36346839
DOI: 10.1126/scisignal.adf6187 -
Golgi Stress Response: New Insights into the Pathogenesis and Therapeutic Targets of Human Diseases.Molecules and Cells Apr 2023The Golgi apparatus modifies and transports secretory and membrane proteins. In some instances, the production of secretory and membrane proteins exceeds the capacity of... (Review)
Review
The Golgi apparatus modifies and transports secretory and membrane proteins. In some instances, the production of secretory and membrane proteins exceeds the capacity of the Golgi apparatus, including vesicle trafficking and the post-translational modification of macromolecules. These proteins are not modified or delivered appropriately due to insufficiency in the Golgi function. These conditions disturb Golgi homeostasis and induce a cellular condition known as Golgi stress, causing cells to activate the 'Golgi stress response,' which is a homeostatic process to increase the capacity of the Golgi based on cellular requirements. Since the Golgi functions are diverse, several response pathways involving TFE3, HSP47, CREB3, proteoglycan, mucin, MAPK/ETS, and PERK regulate the capacity of each Golgi function separately. Understanding the Golgi stress response is crucial for revealing the mechanisms underlying Golgi dynamics and its effect on human health because many signaling molecules are related to diseases, ranging from viral infections to fatal neurodegenerative diseases. Therefore, it is valuable to summarize and investigate the mechanisms underlying Golgi stress response in disease pathogenesis, as they may contribute to developing novel therapeutic strategies. In this review, we investigate the perturbations and stress signaling of the Golgi, as well as the therapeutic potentials of new strategies for treating Golgi stress-associated diseases.
Topics: Humans; Golgi Apparatus; Protein Processing, Post-Translational; Protein Transport; Signal Transduction; Membrane Proteins
PubMed: 36574967
DOI: 10.14348/molcells.2023.2152 -
Cells Feb 2020Membrane and secretory proteins are essential for almost every aspect of cellular function. These proteins are incorporated into ER-derived carriers and transported to... (Review)
Review
Membrane and secretory proteins are essential for almost every aspect of cellular function. These proteins are incorporated into ER-derived carriers and transported to the Golgi before being sorted for delivery to their final destination. Although ER-to-Golgi trafficking is highly conserved among eukaryotes, several layers of complexity have been added to meet the increased demands of complex cell types in metazoans. The specialized morphology of neurons and the necessity for precise spatiotemporal control over membrane and secretory protein localization and function make them particularly vulnerable to defects in trafficking. This review summarizes the general mechanisms involved in ER-to-Golgi trafficking and highlights mutations in genes affecting this process, which are associated with neurological diseases in humans.
Topics: Endoplasmic Reticulum; Golgi Apparatus; Humans; Nervous System Diseases; Protein Transport; Proteins
PubMed: 32053905
DOI: 10.3390/cells9020408