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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 -
The Journal of Cell Biology Jun 2022The mammalian Golgi comprises tightly adjacent and flattened membrane sacs called cisternae. We still do not understand the molecular organization of the Golgi and...
The mammalian Golgi comprises tightly adjacent and flattened membrane sacs called cisternae. We still do not understand the molecular organization of the Golgi and intra-Golgi transport of cargos. One of the most significant challenges to studying the Golgi is resolving Golgi proteins at the cisternal level under light microscopy. We have developed a side-averaging approach to visualize the cisternal organization and intra-Golgi transport in nocodazole-induced Golgi ministacks. Side-view images of ministacks acquired from Airyscan microscopy are transformed and aligned before intensity normalization and averaging. From side-average images of >30 Golgi proteins, we uncovered the organization of the pre-Golgi, cis, medial, trans, and trans-Golgi network membrane with an unprecedented spatial resolution. We observed the progressive transition of a synchronized cargo wave from the cis to the trans-side of the Golgi. Our data support our previous finding, in which constitutive cargos exit at the trans-Golgi while the secretory targeting to the trans-Golgi network is signal dependent.
Topics: Animals; Biological Transport; Golgi Apparatus; Mammals; Nocodazole; trans-Golgi Network
PubMed: 35467701
DOI: 10.1083/jcb.202109114 -
Cells May 2023The Golgi apparatus is an important organelle found in most eukaryotic cells. It plays a vital role in the processing and sorting of proteins, lipids and other cellular... (Review)
Review
The Golgi apparatus is an important organelle found in most eukaryotic cells. It plays a vital role in the processing and sorting of proteins, lipids and other cellular components for delivery to their appropriate destinations within the cell or for secretion outside of the cell. The Golgi complex also plays a role in the regulation of protein trafficking, secretion and post-translational modifications, which are significant in the development and progression of cancer. Abnormalities in this organelle have been observed in various types of cancer, although research into chemotherapies that target the Golgi apparatus is still in its early stages. There are a few promising approaches that are being investigated: (1) Targeting the stimulator of interferon genes protein: The STING pathway senses cytosolic DNA and activates several signaling events. It is regulated by numerous post-translational modifications and relies heavily on vesicular trafficking. Based on some observations which state that a decreased STING expression is present in some cancer cells, agonists for the STING pathway have been developed and are currently being tested in clinical trials, showing encouraging results. (2) Targeting glycosylation: Altered glycosylation, which refers to changes in the carbohydrate molecules that are attached to proteins and lipids in cells, is a common feature of cancer cells, and there are several methods that thwart this process. For example, some inhibitors of glycosylation enzymes have been shown to reduce tumor growth and metastasis in preclinical models of cancer. (3) Targeting Golgi trafficking: The Golgi apparatus is responsible for the sorting and trafficking of proteins within the cell, and disrupting this process may be a potential therapeutic approach for cancer. The unconventional protein secretion is a process that occurs in response to stress and does not require the involvement of the Golgi organelles. P53 is the most frequently altered gene in cancer, dysregulating the normal cellular response to DNA damage. The mutant p53 drives indirectly the upregulation of the Golgi reassembly-stacking protein 55kDa (GRASP55). Through the inhibition of this protein in preclinical models, the reduction of the tumoral growth and metastatic capacity have been obtained successfully. This review supports the hypothesis that the Golgi apparatus may be the target of cytostatic treatment, considering its role in the molecular mechanisms of the neoplastic cells.
Topics: Golgi Apparatus; Neoplasms; Humans; Protein Transport; Glycosylation; Antineoplastic Agents; Tumor Suppressor Protein p53
PubMed: 37296620
DOI: 10.3390/cells12111499 -
The New Phytologist Oct 2023The endomembrane system consists of various membrane-bound organelles including the endoplasmic reticulum (ER), Golgi apparatus, trans-Golgi network (TGN), endosomes,... (Review)
Review
The endomembrane system consists of various membrane-bound organelles including the endoplasmic reticulum (ER), Golgi apparatus, trans-Golgi network (TGN), endosomes, and the lysosome/vacuole. Membrane trafficking between distinct compartments is mainly achieved by vesicular transport. As the endomembrane compartments and the machineries regulating the membrane trafficking are largely conserved across all eukaryotes, our current knowledge on organelle biogenesis and endomembrane trafficking in plants has mainly been shaped by corresponding studies in mammals and yeast. However, unique perspectives have emerged from plant cell biology research through the characterization of plant-specific regulators as well as the development and application of the state-of-the-art microscopical techniques. In this review, we summarize our current knowledge on the plant endomembrane system, with a focus on several distinct pathways: ER-to-Golgi transport, protein sorting at the TGN, endosomal sorting on multivesicular bodies, vacuolar trafficking/vacuole biogenesis, and the autophagy pathway. We also give an update on advanced imaging techniques for the plant cell biology research.
Topics: Plants; Endosomes; Vacuoles; Multivesicular Bodies; Protein Transport; Golgi Apparatus; trans-Golgi Network
PubMed: 37507353
DOI: 10.1111/nph.19134 -
BMB Reports May 2021The Golgi complex plays a central role in protein secretion by regulating cargo sorting and trafficking. As these processes are of functional importance to cell... (Review)
Review
The Golgi complex plays a central role in protein secretion by regulating cargo sorting and trafficking. As these processes are of functional importance to cell polarity, motility, growth, and division, there is considerable interest in achieving a comprehensive understanding of Golgi complex biology. However, the unique stack structure of this organelle has been a major hurdle to our understanding of how proteins are secreted through the Golgi apparatus. Herein, we summarize available relevant research to gain an understanding of protein secretion via the Golgi complex. This includes the molecular mechanisms of intra-Golgi trafficking and cargo export in the trans-Golgi network. Moreover, we review recent insights on signaling pathways regulated by the Golgi complex and their physiological significance. [BMB Reports 2021; 54(5): 246-252].
Topics: Golgi Apparatus; Humans; Proteins
PubMed: 33612152
DOI: 10.5483/BMBRep.2021.54.5.270 -
Methods in Molecular Biology (Clifton,... 2023The Golgi is a complex structure characterized by stacks of tightly aligned flat cisternae. In mammalian cells, Golgi stacks often concentrate in the perinuclear region...
The Golgi is a complex structure characterized by stacks of tightly aligned flat cisternae. In mammalian cells, Golgi stacks often concentrate in the perinuclear region and link together to form a ribbon. This structure is dynamic to accommodate continuous cargo flow in and out of the Golgi in both directions and undergoes morphological changes under physiological and pathological conditions. The fine, stacked Golgi structure makes it difficult to study by conventional light or even super-resolution microscopy. Furthermore, efforts to understand how Golgi structural dynamics impact cellular processes have been slow because of the knowledge gap in the protein machinery that maintains the complex and dynamic Golgi structure. In this method article, we list the common assays used in our research to help new and established researchers select the most appropriate method to properly address their questions.
Topics: Animals; Golgi Apparatus; Mammals
PubMed: 36512224
DOI: 10.1007/978-1-0716-2639-9_20 -
Plant Physiology and Biochemistry : PPB Dec 2021The organelles of the secretory pathway are characterized by specific organization and function but they communicate in different ways with intense functional crosstalk.... (Review)
Review
The organelles of the secretory pathway are characterized by specific organization and function but they communicate in different ways with intense functional crosstalk. The best known membrane-bound transport carriers are known as protein-coated vesicles. Other traffic mechanisms, despite the intense investigations, still show incongruences. The review intends to provide a general view of the mechanisms involved in membrane traffic. We evidence that organelles' biogenesis involves mechanisms that actively operate during the entire cell cycle and the persistent interconnections between the Endoplasmic reticulum (ER), Golgi apparatus, trans-Golgi network (TGN) and endosomes, the vacuolar complex and the plasma membrane (PM) may be seen as a very dynamic membrane network in which vesicular traffic is part of a general maturation process.
Topics: Cell Membrane; Endoplasmic Reticulum; Golgi Apparatus; Plant Cells; Protein Transport; trans-Golgi Network
PubMed: 34775176
DOI: 10.1016/j.plaphy.2021.11.003 -
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 -
Cells Apr 2022The Golgi apparatus is at the center of protein processing and trafficking in normal cells. Under pathological conditions, such as in cancer, aberrant Golgi dynamics... (Review)
Review
The Golgi apparatus is at the center of protein processing and trafficking in normal cells. Under pathological conditions, such as in cancer, aberrant Golgi dynamics alter the tumor microenvironment and the immune landscape, which enhances the invasive and metastatic potential of cancer cells. Among these changes in the Golgi in cancer include altered Golgi orientation and morphology that contribute to atypical Golgi function in protein trafficking, post-translational modification, and exocytosis. Golgi-associated gene mutations are ubiquitous across most cancers and are responsible for modifying Golgi function to become pro-metastatic. The pharmacological targeting of the Golgi or its associated genes has been difficult in the clinic; thus, studying the Golgi and its role in cancer is critical to developing novel therapeutic agents that limit cancer progression and metastasis. In this review, we aim to discuss how disrupted Golgi function in cancer cells promotes invasion and metastasis.
Topics: Golgi Apparatus; Humans; Neoplasms; Protein Transport; Tumor Microenvironment
PubMed: 35563790
DOI: 10.3390/cells11091484 -
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