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Journal of Microscopy Nov 2020The plant Golgi apparatus (sensu lato: Golgi stack + Trans Golgi Network, TGN) is a highly polar and mobile key organelle lying at the junction of the secretory and... (Review)
Review
The plant Golgi apparatus (sensu lato: Golgi stack + Trans Golgi Network, TGN) is a highly polar and mobile key organelle lying at the junction of the secretory and endocytic pathways. Unlike its counterpart in animal cells it does not disassemble during mitosis. It modifies glycoproteins sent to it from the endoplasmic reticulum (ER), it recycles ER resident proteins, it sorts proteins destined for the vacuole from secretory proteins, it receives proteins internalised from the plasma membrane and either recycles them to the plasma membrane or retargets them to the vacuole for degradation. In functional terms the Golgi apparatus can be likened to a car factory, with incoming (COPII traffic) and returning (COPI traffic) railway lines at the entry gate, and a distribution centre (the TGN) at the exit gate of the assembly hall. In the assembly hall we have a conveyor belt system where the incoming car parts are initially assembled (in the cis-area) then gradually modified into different models (processing of secretory cargo) as the cars pass along the production line (cisternal maturation). After being released the trans-area, the cars (secretory cargos) are moved out of the assembly hall and passed on to the distribution centre (TGN), where the various models are placed onto different trains (cargo sorting into carrier vesicles) for transport to the car dealers. Cars with motor problems are returned to the factory for repairs (endocytosis to the TGN). This simple analogy also incorporates features of quality control at the COPII entry gate with defective parts being returned to the manufacturing center (the ER) via the COPI trains (vesicles). In recent years, numerous studies have contributed to our knowledge on Golgi function and structure in both animals, yeast and plants. This review, rather than giving a balanced account of the structure as well as of the function of the Golgi apparatus has purposely a marked slant towards plant Golgi ultrastructure integrating findings from the mammalian/animal field.
Topics: Coated Vesicles; Endoplasmic Reticulum; Golgi Apparatus; Microscopy, Electron; Plant Cells; Secretory Vesicles; Transport Vesicles; trans-Golgi Network
PubMed: 32420623
DOI: 10.1111/jmi.12899 -
Cells Jun 2020Cellular secretion depends on exocytosis of secretory vesicles and discharge of vesicle contents. Actin and myosin are essential for pre-fusion and post-fusion stages of... (Review)
Review
Cellular secretion depends on exocytosis of secretory vesicles and discharge of vesicle contents. Actin and myosin are essential for pre-fusion and post-fusion stages of exocytosis. Secretory vesicles depend on actin for transport to and attachment at the cell cortex during the pre-fusion phase. Actin coats on fused vesicles contribute to stabilization of large vesicles, active vesicle contraction and/or retrieval of excess membrane during the post-fusion phase. Myosin molecular motors complement the role of actin. Myosin V is required for vesicle trafficking and attachment to cortical actin. Myosin I and II members engage in local remodeling of cortical actin to allow vesicles to get access to the plasma membrane for membrane fusion. Myosins stabilize open fusion pores and contribute to anchoring and contraction of actin coats to facilitate vesicle content release. Actin and myosin function in secretion is regulated by a plethora of interacting regulatory lipids and proteins. Some of these processes have been first described in non-neuronal cells and reflect adaptations to exocytosis of large secretory vesicles and/or secretion of bulky vesicle cargoes. Here we collate the current knowledge and highlight the role of actomyosin during distinct phases of exocytosis in an attempt to identify unifying molecular mechanisms in non-neuronal secretory cells.
Topics: Actin Cytoskeleton; Actins; Animals; Exocytosis; Humans; Membrane Fusion; Myosins; Secretory Vesicles
PubMed: 32545391
DOI: 10.3390/cells9061455 -
Journal of Cell Science May 2023The formation of membrane vesicles is a common feature in all eukaryotes. Lipid rafts are the best-studied example of membrane domains for both eukaryotes and... (Review)
Review
The formation of membrane vesicles is a common feature in all eukaryotes. Lipid rafts are the best-studied example of membrane domains for both eukaryotes and prokaryotes, and their existence also is suggested in Archaea membranes. Lipid rafts are involved in the formation of transport vesicles, endocytic vesicles, exocytic vesicles, synaptic vesicles and extracellular vesicles, as well as enveloped viruses. Two mechanisms of how rafts are involved in vesicle formation have been proposed: first, that raft proteins and/or lipids located in lipid rafts associate with coat proteins that form a budding vesicle, and second, vesicle budding is triggered by enzymatic generation of cone-shaped ceramides and inverted cone-shaped lyso-phospholipids. In both cases, induction of curvature is also facilitated by the relaxation of tension in the raft domain. In this Review, we discuss the role of raft-derived vesicles in several intracellular trafficking pathways. We also highlight their role in different pathways of endocytosis, and in the formation of intraluminal vesicles (ILVs) through budding inwards from the multivesicular body (MVB) membrane, because rafts inside MVB membranes are likely to be involved in loading RNA into ILVs. Finally, we discuss the association of glycoproteins with rafts via the glycocalyx.
Topics: Endocytosis; Membrane Microdomains; Cell Division; Ceramides; Eukaryota
PubMed: 37158681
DOI: 10.1242/jcs.260887 -
Journal of Liposome Research Mar 2021Vesicle structures primarily embody spherical capsules composed of a single or multiple bilayers, entrapping a pool of aqueous solution in their interior. The bilayers... (Review)
Review
Vesicle structures primarily embody spherical capsules composed of a single or multiple bilayers, entrapping a pool of aqueous solution in their interior. The bilayers can be synthesised by phospholipids or other amphiphiles (surfactants, block copolymers, etc.). Vesicles with broad-spectrum applications in numerous scientific disciplines, including biochemistry, biophysics, biology, and various pharmaceutical industries, have attracted widespread attention. Consequently, a multitude of protocols have been devised and proposed for their fabrication. In this review, with a motivation to derive the basic conditions for the formation of vesicles, the associated thermodynamic and kinetic aspects are comprehensively appraised. Contextually, an all-purpose overview of the underlying thermodynamics of bilayer/membrane generation and deformation, including the chemical potential of aggregates, geometric packing and the concept of elastic properties, is presented. Additionally, the current review highlights the probable, inherent mechanisms of vesicle formation under distinct modes of manufacturing. We lay focus on vesicle formation from pre-existing bilayers, as well as from bilayers, which form when lipids from an organic solvent are transferred into an aqueous medium. Furthermore, we outline the kinetic effects on vesicle formation from the lamellar phase, with and without the presence of shearing force. Wherever required, the experimental and/or theoretical outcomes, the driving forces for vesicle size selection, and various scaling laws are also reviewed, all of which facilitate an overall improved understanding of the vesicle formation mechanisms.
Topics: Kinetics; Lipid Bilayers; Liposomes; Thermodynamics
PubMed: 32066297
DOI: 10.1080/08982104.2020.1730401 -
Pharmaceutics Nov 2022Neurological diseases remain some of the major causes of death and disability in the world. Few types of drugs and insufficient delivery across the blood-brain barrier... (Review)
Review
Neurological diseases remain some of the major causes of death and disability in the world. Few types of drugs and insufficient delivery across the blood-brain barrier limit the treatment of neurological disorders. The past two decades have seen the rapid development of extracellular vesicle-based therapeutics in many fields. As the physiological and pathophysiological roles of extracellular vesicles are recognized in neurological diseases, they have become promising therapeutics and targets for therapeutic interventions. Moreover, advanced nanomedicine technologies have explored the potential of extracellular vesicles as drug delivery systems in neurological diseases. In this review, we discussed the preclinical strategies for extracellular vesicle-based therapeutics in neurological disorders and the struggles involved in their clinical application.
PubMed: 36559145
DOI: 10.3390/pharmaceutics14122652 -
Journal of Leukocyte Biology Oct 2023Systemic juvenile idiopathic arthritis is a chronic pediatric inflammatory disease of unknown etiology, characterized by fever, rash, hepatosplenomegaly, serositis, and...
Systemic juvenile idiopathic arthritis is a chronic pediatric inflammatory disease of unknown etiology, characterized by fever, rash, hepatosplenomegaly, serositis, and arthritis. We hypothesized that intercellular communication, mediated by extracellular vesicles, contributes to systemic juvenile idiopathic arthritis pathogenesis and that the number and cellular sources of extracellular vesicles would differ between inactive and active states of systemic juvenile idiopathic arthritis and healthy controls. We evaluated plasma from healthy pediatric controls and patients with systemic juvenile idiopathic arthritis with active systemic flare or inactive disease. We isolated extracellular vesicles by size exclusion chromatography and determined total extracellular vesicle abundance and size distribution using microfluidic resistive pulse sensing. Cell-specific extracellular vesicle subpopulations were measured by nanoscale flow cytometry. Isolated extracellular vesicles were validated using a variety of ways, including nanotracking and cryo-electron microscopy. Extracellular vesicle protein content was analyzed in pooled samples using mass spectrometry. Total extracellular vesicle concentration did not significantly differ between controls and patients with systemic juvenile idiopathic arthritis. Extracellular vesicles with diameters <200 nm were the most abundant, including the majority of cell-specific extracellular vesicle subpopulations. Patients with systemic juvenile idiopathic arthritis had significantly higher levels of extracellular vesicles from activated platelets, intermediate monocytes, and chronically activated endothelial cells, with the latter significantly more elevated in active systemic juvenile idiopathic arthritis relative to inactive disease and controls. Protein analysis of isolated extracellular vesicles from active patients showed a proinflammatory profile, uniquely expressing heat shock protein 47, a stress-inducible protein. Our findings indicate that multiple cell types contribute to altered extracellular vesicle profiles in systemic juvenile idiopathic arthritis. The extracellular vesicle differences between systemic juvenile idiopathic arthritis disease states and healthy controls implicate extracellular vesicle-mediated cellular crosstalk as a potential driver of systemic juvenile idiopathic arthritis disease activity.
Topics: Humans; Child; Arthritis, Juvenile; Cryoelectron Microscopy; Endothelial Cells; Monocytes; Extracellular Vesicles
PubMed: 37201912
DOI: 10.1093/jleuko/qiad059 -
Frontiers in Cardiovascular Medicine 2022Cardiovascular diseases rank the highest incidence and mortality worldwide. As the most common type of cardiovascular disease, myocardial infarction causes high... (Review)
Review
Cardiovascular diseases rank the highest incidence and mortality worldwide. As the most common type of cardiovascular disease, myocardial infarction causes high morbidity and mortality. Recent studies have revealed that extracellular vesicles, including exosomes, show great potential as a promising cell-free therapy for the treatment of myocardial infarction. However, low heart-targeting efficiency and short plasma half-life have hampered the clinical translation of extracellular vesicle therapy. Currently, four major types of strategies aiming at enhancing target efficiency have been developed, including modifying EV surface, suppressing non-target absorption, increasing the uptake efficiency of target cells, and utilizing a hydrogel patch. This presented review summarizes the current research aimed at EV heart targeting and discusses the challenges and opportunities in EV therapy, which will be beneficial for the development of effective heart-targeting strategies.
PubMed: 36704471
DOI: 10.3389/fcvm.2022.1041481 -
Acta Neuropathologica Apr 2021The neuronal protein α-synuclein (αS) is central to the pathogenesis of Parkinson's disease and other progressive brain diseases such as Lewy body dementia and... (Review)
Review
The neuronal protein α-synuclein (αS) is central to the pathogenesis of Parkinson's disease and other progressive brain diseases such as Lewy body dementia and multiple system atrophy. These diseases, collectively referred to as 'synucleinopathies', have long been considered purely proteinopathies: diseases characterized by the misfolding of a protein into small and large aggregates mainly consisting of that protein (in this case: α-synuclein). However, recent morphological insights into Lewy bodies, the hallmark neuropathology of human synucleinopathies, suggests these lesions are also rich in vesicles and other membranous organelles. Moreover, αS physiology and pathology are both strongly associated with various aspects of intracellular vesicle trafficking and lipid biology. αS physiologically binds to synaptic and other small vesicles, and several functions of αS in regulating vesicle biology have been proposed. Familial PD-linked αS excess and missense mutations have been shown to impair vesicle trafficking and alter lipid homeostasis. On the other hand, vesicle trafficking and lipid-related genes have emerged as Parkinson's risk factors, suggesting a bidirectional relationship. The answer to the question "Does abnormal αS accumulation cause impaired vesicle trafficking and lipid dyshomeostasis or is αS aggregation the consequence of such impairments?" may be "Both". Here, we review current knowledge of the αS-lipid and αS-vesicle trafficking interplay, with a special focus on Parkinson's disease and Lewy body dementia.
Topics: Animals; Cytoplasmic Vesicles; Humans; Lipid Metabolism; Protein Aggregation, Pathological; Protein Transport; Synucleinopathies; alpha-Synuclein
PubMed: 32607605
DOI: 10.1007/s00401-020-02177-z -
Trends in Neurosciences Jul 2021The concentration of calcium ions in presynaptic terminals regulates transmitter release, but underlying mechanisms have remained unclear. Here we review recent studies... (Review)
Review
The concentration of calcium ions in presynaptic terminals regulates transmitter release, but underlying mechanisms have remained unclear. Here we review recent studies that shed new light on this issue. Fast-freezing electron microscopy and total internal reflection fluorescence microscopy studies reveal complex calcium-dependent vesicle movements including docking on a millisecond time scale. Recordings from so-called 'simple synapses' indicate that calcium not only triggers exocytosis, but also modifies synaptic strength by controlling a final, rapid vesicle maturation step before release. Molecular studies identify several calcium-sensitive domains on Munc13 and on synaptotagmin-1 that are likely involved in bringing the vesicular and plasma membranes closer together in response to calcium elevation. Together, these results suggest that calcium-dependent vesicle docking occurs in a wide range of time domains and plays a crucial role in several phenomena including synaptic facilitation, post-tetanic potentiation, and neuromodulator-induced potentiation.
Topics: Calcium; Exocytosis; Humans; Presynaptic Terminals; Synaptic Transmission; Synaptic Vesicles
PubMed: 34049722
DOI: 10.1016/j.tins.2021.04.003 -
Biomedicines Jul 2022Within 1 millisecond of action potential arrival at presynaptic terminals voltage-gated Ca channels open. The Ca channels are linked to synaptic vesicles which are... (Review)
Review
Within 1 millisecond of action potential arrival at presynaptic terminals voltage-gated Ca channels open. The Ca channels are linked to synaptic vesicles which are tethered by active zone proteins. Ca entrance into the active zone triggers: (1) the fusion of the vesicle and exocytosis, (2) the replenishment of the active zone with vesicles for incoming exocytosis, and (3) various types of endocytosis for vesicle reuse, dependent on the pattern of firing. These time-dependent vesicle dynamics are controlled by presynaptic Ca sensor proteins, regulating active zone scaffold proteins, fusion machinery proteins, motor proteins, endocytic proteins, several enzymes, and even Ca channels, following the decay of Ca concentration after the action potential. Here, I summarize the Ca-dependent protein controls of synchronous and asynchronous vesicle release, rapid replenishment of the active zone, endocytosis, and short-term plasticity within 100 msec after the action potential. Furthermore, I discuss the contribution of active zone proteins to presynaptic plasticity and to homeostatic readjustment during and after intense activity, in addition to activity-dependent endocytosis.
PubMed: 35884898
DOI: 10.3390/biomedicines10071593