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ACS Nano Nov 2023Innate and adaptive immunity is important for initiating and maintaining immune function. The nucleotide-binding oligomerization domain-like receptor family pyrin...
Innate and adaptive immunity is important for initiating and maintaining immune function. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome serves as a checkpoint in innate and adaptive immunity, promoting the secretion of pro-inflammatory cytokines and gasdermin D-mediated pyroptosis. As a highly inflammatory form of cell death distinct from apoptosis, pyroptosis can trigger immunogenic cell death and promote systemic immune responses in solid tumors. Previous studies proposed that NLRP3 was activated by translocation to the mitochondria. However, a recent authoritative study has challenged this model and proved that the Golgi apparatus might be a prerequisite for the activation of NLRP3. In this study, we first developed a Golgi apparatus-targeted photodynamic strategy to induce the activation of NLRP3 by precisely locating organelles. We found that Golgi apparatus-targeted photodynamic therapy could significantly upregulate NLRP3 expression to promote the subsequent release of intracellular proinflammatory contents such as IL-1β or IL-18, creating an inflammatory storm to enhance innate immunity. Moreover, this acute NLRP3 upregulation also activated its downstream classical caspase-1-dependent pyroptosis to enhance tumor immunogenicity, triggering adaptive immunity. Pyroptosis eventually led to immunogenic cell death, promoted the maturation of dendritic cells, and effectively activated antitumor immunity and long-lived immune memory. Overall, this Golgi apparatus-targeted strategy provided molecular insights into the occurrence of immunogenic pyroptosis and offered a platform to remodel the tumor microenvironment.
Topics: NLR Family, Pyrin Domain-Containing 3 Protein; Pyroptosis; Inflammasomes; Immunity, Innate; Golgi Apparatus; Interleukin-1beta; Caspase 1
PubMed: 37921421
DOI: 10.1021/acsnano.3c05005 -
International Journal of Biological... Dec 2020Golgi Reassembly and Stacking Proteins (GRASPs) were firstly described as crucial elements in determining the structure of the Golgi complex. However, data have been... (Review)
Review
Golgi Reassembly and Stacking Proteins (GRASPs) were firstly described as crucial elements in determining the structure of the Golgi complex. However, data have been accumulating over the years showing GRASPs can participate in various cell processes beyond the Golgi maintenance, including cell adhesion and migration, autophagy and unconventional secretion of proteins. A comprehensive understanding of the GRASP functions requires deep mechanistic knowledge of its structure and dynamics, especially because of the unique structural plasticity observed for many members of this family coupled with their high promiscuity in mediating protein-protein interactions. Here, we critically review data regarding the structural biophysics of GRASPs in the quest for understanding the structural determinants of different functionalities. We dissect GRASP structure starting with the full-length protein down to its separate domains (PDZ1, PDZ2 and SPR) and outline some structural features common to all members of the GRASP family (such as the presence of many intrinsically disordered regions). Although the impact of those exquisite properties in vivo will still require further studies, it is possible, from our review, to pinpoint factors that must be considered in future interpretation of data regarding GRASP functions, thus bringing somewhat new perspectives to the field.
Topics: Biophysics; Crystallography, X-Ray; Golgi Apparatus; Golgi Matrix Proteins; Humans; Membrane Proteins; Protein Conformation
PubMed: 32871120
DOI: 10.1016/j.ijbiomac.2020.08.203 -
Current Opinion in Cell Biology Apr 2019Meticulous observations of the cell perinuclear region where the Golgi and the endoplasmic reticulum (ER) networks intermingle have revealed close contact sites of... (Review)
Review
Meticulous observations of the cell perinuclear region where the Golgi and the endoplasmic reticulum (ER) networks intermingle have revealed close contact sites of barely 20 nm between these two organelles. Recent studies demonstrate that molecular machineries, including lipid-transfer proteins, enriched in membrane contact sites between ER and trans-Golgi are capable of bridging membranes and exchanging key lipids such as sphingolipid precursors and cholesterol while bypassing the early secretory compartments. This occurs at the cost of an intense phosphoinositide turnover in order to prepare a membrane environment conducive to the signaling and trafficking functions of the trans-Golgi network. A tight control operates in the contact zone to adjust lipid transport and metabolism to the cellular needs.
Topics: Animals; Biological Transport; Carrier Proteins; Endoplasmic Reticulum; Golgi Apparatus; Humans; Lipid Metabolism; Mitochondrial Membranes; Protein Transport; Signal Transduction; trans-Golgi Network
PubMed: 30390465
DOI: 10.1016/j.ceb.2018.10.002 -
Cell Biology International Sep 2022The Golgi apparatus is a membrane-bound organelle that functions as a central role in the secretory pathway. Since the discovery of the Golgi apparatus, its structure... (Review)
Review
The Golgi apparatus is a membrane-bound organelle that functions as a central role in the secretory pathway. Since the discovery of the Golgi apparatus, its structure and function have attracted ever-increasing attention from researchers. Recently, it has been demonstrated that metal ions are necessary for the Golgi apparatus to maintain its proper structure and functions. Given that metal ions play an important role in various biological processes, their abnormal homeostasis is related to many diseases. Therefore, in this paper, we reviewed the uptake and release mechanisms of the Golgi apparatus Ca , Cu, and Zn . Furthermore, we describe the diseases associated with Golgi apparatus Ca , Cu, and Zn imbalance.
Topics: Biological Transport; Calcium; Golgi Apparatus; Ions
PubMed: 35830695
DOI: 10.1002/cbin.11848 -
Advances in Experimental Medicine and... 2017The lateral transfer of photosynthesis between kingdoms through endosymbiosis is among the most spectacular examples of evolutionary innovation. Euglena, which acquired... (Review)
Review
The lateral transfer of photosynthesis between kingdoms through endosymbiosis is among the most spectacular examples of evolutionary innovation. Euglena, which acquired a chloroplast indirectly through an endosymbiosis with a green alga, represents such an example. As with other endosymbiont-derived plastids from eukaryotes, there are additional membranes that surround the organelle, of which Euglena has three. Thus, photosynthetic genes that were transferred from the endosymbiont to the host nucleus and whose proteins are required in the new plastid, are now faced with targeting and plastid import challenges. Early immunoelectron microscopy data suggested that the light-harvesting complexes, photosynthetic proteins in the thylakoid membrane, are post-translationally targeted to the plastid via the Golgi apparatus, an unexpected discovery at the time. Proteins targeted to the Euglena plastid have complex, bipartite presequences that direct them into the endomembrane system, through the Golgi apparatus and ultimately on to the plastid, presumably via transport vesicles. From transcriptome sequencing, dozens of plastid-targeted proteins were identified, leading to the identification of two different presequence structures. Both have an amino terminal signal peptide followed by a transit peptide for plastid import, but only one of the two classes of presequences has a third domain-the stop transfer sequence. This discovery implied two different transport mechanisms; one where the protein was fully inserted into the lumen of the ER and another where the protein remains attached to, but effectively outside, the endomembrane system. In this review, we will discuss the biochemical and bioinformatic evidence for plastid targeting, discuss the evolution of the targeting system, and ultimately provide a working model for the targeting and import of proteins into the plastid of Euglena.
Topics: Euglena; Golgi Apparatus; Intracellular Membranes; Protein Transport; Protozoan Proteins; Thylakoids
PubMed: 28429323
DOI: 10.1007/978-3-319-54910-1_10 -
Journal of Cellular Physiology Apr 2018The Golgi apparatus (GA) is a ribbon-like system of stacks which consist of multiple closely apposed flattened cisternae and vesicles usually localized in the... (Review)
Review
The Golgi apparatus (GA) is a ribbon-like system of stacks which consist of multiple closely apposed flattened cisternae and vesicles usually localized in the juxta-nuclear area. As for the biological functions, the GA plays a major role in protein biosynthesis, post-translational modification, and sorting protein from ER to plasma membrane and other destinations. Structural changes and functional disorder of the GA is associated with various diseases. Moreover, increasing evidence revealed that swelling, poor development, and other morphological alterations of the GA are linked to cardiovascular diseases such as heart failure (HF), arrhythmia, and dilated cardiomyopathy. Furthermore, dysfunction of the GA is also related to cardiovascular diseases since the GA is extremely responsible for transport, glycosylation, biosynthesis, and subcellular distribution of cardiovascular proteins. This review gives a brief overview of the intricate relationship between the GA and cardiovascular diseases. In addition, we provide a further prospective that the GA may provide diagnosis reference for cardiovascular diseases, and changes in the ultrastructure and morphology of the GA such as swelling, poor development, and fragmentation may serve as a reliable index for cardiovascular diseases.
Topics: Animals; Cardiovascular Diseases; Glycosylation; Golgi Apparatus; Humans; Models, Biological; Proteins
PubMed: 28574583
DOI: 10.1002/jcp.26039 -
Tissue & Cell Apr 2017The Golgi apparatus is a central organelle of the secretory pathway involved in the post-translational modification and sorting of lipids and proteins. In mammalian... (Review)
Review
The Golgi apparatus is a central organelle of the secretory pathway involved in the post-translational modification and sorting of lipids and proteins. In mammalian cells, the Golgi apparatus is composed of stacks of cisternae organized in polarized manner, which are interconnected by membrane tubules to constitute the Golgi ribbon, located in the proximity of the centrosome. Besides the processing and transport of cargo, the Golgi complex is actively involved in the regulation of mitotic entry, cytoskeleton organization and dynamics, calcium homeostasis, and apoptosis, representing a signalling platform for the control of several cellular functions, including signalling initiated by receptors located at the plasma membrane. Alterations of the conventional Golgi organization are associated to many disorders, such as cancer or different neurodegenerative diseases. In this review, we examine the functional implications of modifications of Golgi structure in neurodegenerative disorders, with a focus on the role of Golgi fragmentation in the development of Alzheimer's disease. The comprehension of the mechanism that induces Golgi fragmentation and of its downstream effects on neuronal function have the potential to contribute to the development of more effective therapies to treat or prevent some of these disorders.
Topics: Alzheimer Disease; Apoptosis; Calcium Signaling; Cell Membrane; Golgi Apparatus; Humans; Neurons; Protein Processing, Post-Translational; Protein Transport
PubMed: 27894594
DOI: 10.1016/j.tice.2016.11.007 -
Biology of the Cell Oct 2017The Golgi apparatus plays essential roles in the processing and sorting of proteins and lipids, but it can also act as a signalling hub and a microtubule-nucleation... (Review)
Review
The Golgi apparatus plays essential roles in the processing and sorting of proteins and lipids, but it can also act as a signalling hub and a microtubule-nucleation centre. The Golgi complex (GC) of mammalian cells is composed of stacks connected by tubular bridges to form a continuous membranous system. In spite of this structural complexity, the GC is highly dynamic, and this feature becomes particularly evident during mitosis, when the GC undergoes a multi-step disassembly process that allows its correct partitioning and inheritance by daughter cells. Strikingly, different steps of Golgi disassembly control mitotic entry and progression, indicating that cells actively monitor Golgi integrity during cell division. Here, we summarise the basic mechanisms and the molecular players that are involved in Golgi disassembly, focussing in particular on recent studies that have revealed the fundamental signalling pathways that connect Golgi inheritance to mitotic entry and progression.
Topics: Animals; Cell Cycle; Cell Division; Golgi Apparatus; Humans; Mitosis; Spindle Apparatus
PubMed: 28799169
DOI: 10.1111/boc.201700032 -
Physical Biology Sep 2019The Golgi apparatus has intrigued researchers since its discovery and despite the advances, there are still many open questions in regards to its shape and function. We...
The Golgi apparatus has intrigued researchers since its discovery and despite the advances, there are still many open questions in regards to its shape and function. We propose a mechanical model of Golgi apparatus stack and explain its most elementary geometrical properties: the equilibrium number of cisternae, the stack size, and its general equilibrium shape. Combining both analytical and numerical methods we successfully reconstruct the stack morphology within the theory of bending elasticity. We demonstrate that energy-wise the stack prefers an overall bent shape and show strong evidence that the adhesion strength determines the equilibrium number of cisternae per stack. We explore the morphological role of fenestrations and discuss their impact on the overall stack structure. We also comment on the effects of the asymmetry in the composition of membrane leaflets on the shape of the cisternae and thus offer a broad steady-state study of the stack morphology and present a method that can be used also for other membrane-bound organelles.
Topics: Biomechanical Phenomena; Elasticity; Golgi Apparatus; Models, Biological
PubMed: 31365910
DOI: 10.1088/1478-3975/ab3766 -
BioFactors (Oxford, England) Nov 2021The organelle of eukaryotes is a finely regulated system. Once disturbed, it activates the specific autoregulatory systems, namely, organelle autoregulation. Among... (Review)
Review
The organelle of eukaryotes is a finely regulated system. Once disturbed, it activates the specific autoregulatory systems, namely, organelle autoregulation. Among which, the Golgi stress response accounts for one. When the abundance and capacity of the Golgi apparatus are insufficient compared with cellular demand, the Golgi stress response is activated to enhance the function of the Golgi apparatus. Although the molecular mechanism of the Golgi stress response has not been well characterized yet, it seems to be an important part of the mammalian stress response. In this review, we discuss the current status of research on the six pathways of the mammalian Golgi stress response (the TFE3, heat shock protein 47, CREB3, E26 transformation specific, proteoglycan, and mucin pathways), which regulate the general function of the Golgi apparatus, anti-apoptosis, pro-apoptosis, proteoglycan glycosylation, and mucin glycosylation, respectively.
Topics: Golgi Apparatus; HeLa Cells; Homeostasis; Humans; Mucins; Stress, Physiological
PubMed: 34500494
DOI: 10.1002/biof.1780