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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 -
Mycologia 2016Cargo passage through the Golgi, albeit an undoubtedly essential cellular function, is a mechanistically unresolved and much debated process. Although the main molecular... (Review)
Review
Cargo passage through the Golgi, albeit an undoubtedly essential cellular function, is a mechanistically unresolved and much debated process. Although the main molecular players are conserved, diversification of the Golgi among different eukaryotic lineages is providing us with tools to resolve standing controversies. During the past decade the Golgi apparatus of model filamentous fungi, mainly Aspergillus nidulans, has been intensively studied. Here an overview of the most important findings in the field is provided. Golgi architecture and dynamics, as well as the novel cell biology tools that were developed in filamentous fungi in these studies, are addressed. An emphasis is placed on the central role the Golgi has as a crossroads in the endocytic and secretory-traffic pathways in hyphae. Finally the major advances that the A. nidulans Golgi biology has yielded so far regarding our understanding of key Golgi regulators, such as the Rab GTPases RabC(Rab6) and RabE(Rab11), the oligomeric transport protein particle, TRAPPII, and the Golgi guanine nucleotide exchange factors of Arf1, GeaA(GBF1/Gea1) and HypB(BIG/Sec7), are highlighted.
Topics: Aspergillus nidulans; Fungal Proteins; Golgi Apparatus; Hyphae
PubMed: 26932185
DOI: 10.3852/15-309 -
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 -
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 -
Results and Problems in Cell... 2019The role of the Golgi apparatus in carcinogenesis still remains unclear. A number of structural and functional cis-, medial-, and trans-Golgi proteins as well as a... (Review)
Review
The role of the Golgi apparatus in carcinogenesis still remains unclear. A number of structural and functional cis-, medial-, and trans-Golgi proteins as well as a complexity of metabolic pathways which they mediate may indicate a central role of the Golgi apparatus in the development and progression of cancer. Pleiotropy of cellular function of the Golgi apparatus makes it a "metabolic heart" or a relay station of a cell, which combines multiple signaling pathways involved in carcinogenesis. Therefore, any damage to or structural abnormality of the Golgi apparatus, causing its fragmentation and/or biochemical dysregulation, results in an up- or downregulation of signaling pathways and may in turn promote tumor progression, as well as local nodal and distant metastases. Three alternative or parallel models of spatial and functional Golgi organization within tumor cells were proposed: (1) compacted Golgi structure, (2) normal Golgi structure with its increased activity, and (3) the Golgi fragmentation with ministacks formation. Regardless of the assumed model, the increased activity of oncogenesis initiators and promoters with inhibition of suppressor proteins results in an increased cell motility and migration, increased angiogenesis, significantly activated trafficking kinetics, proliferation, EMT induction, decreased susceptibility to apoptosis-inducing factors, and modulating immune response to tumor cell antigens. Eventually, this will lead to the increased metastatic potential of cancer cells and an increased risk of lymph node and distant metastases. This chapter provided an overview of the current state of knowledge of selected Golgi proteins, their role in cytophysiology as well as potential involvement in tumorigenesis.
Topics: Carcinogenesis; Cell Movement; Golgi Apparatus; Humans; Neoplasms; Signal Transduction
PubMed: 31435808
DOI: 10.1007/978-3-030-23173-6_20 -
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 -
Current Opinion in Cell Biology Feb 2018The Golgi complex occupies a strategic position in the endomembrane system and acts not only as a key trafficking and sorting station and a vital biosynthetic center for... (Review)
Review
The Golgi complex occupies a strategic position in the endomembrane system and acts not only as a key trafficking and sorting station and a vital biosynthetic center for glycoproteins and lipids, but also as an active signaling hub. As such, the Golgi complex participates in the establishment and maintenance of cell compartmentalization and in general, cell processes such as cell growth and apoptosis. The different functions of the Golgi complex are executed by composite molecular machineries that have been exhaustively dissected over the last three decades. These machineries can become dysfunctional as a result of mutations in the respective encoding genes or may be hijacked by infectious agents or misregulated in the course of multifactorial diseases such as neurodegeneration and cancer. Small molecules targeting components of these machineries have been instrumental in dissecting their functions in in vitro studies and some of them have been developed or are currently under development for clinical use.
Topics: Animals; Disease; Drug Therapy; Golgi Apparatus; Humans; Pathology; Protein Transport; Signal Transduction
PubMed: 29614425
DOI: 10.1016/j.ceb.2018.03.005 -
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 -
Trends in Cell Biology Jun 2020The Golgi apparatus serves as a receiving station where proteins from the endoplasmic reticulum (ER) are further processed before being sent to other cellular... (Review)
Review
The Golgi apparatus serves as a receiving station where proteins from the endoplasmic reticulum (ER) are further processed before being sent to other cellular compartments. In addition to its well-appreciated roles in vesicular trafficking and protein/lipid secretion, recent studies have demonstrated that the Golgi acts as a signaling platform to facilitate multiple innate immune pathways. Moreover, the membranous networks that connect the Golgi with the ER, mitochondria, endosomes, and autophagosomes provide convenient access to innate immune signal transduction and subsequent effector responses. Here, we review the emerging knowledge about the roles of the Golgi in the initiation and activation of innate immune signaling. Moreover, microbial hijacking strategies that inhibit Golgi-associated innate immune responses will also be discussed.
Topics: Animals; Bacteria; Golgi Apparatus; Humans; Immunity, Innate; Inflammasomes; Models, Biological
PubMed: 32413316
DOI: 10.1016/j.tcb.2020.02.008