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Cells Sep 2023The faithful formation and, consequently, function of a synapse requires continuous and tightly controlled delivery of synaptic material. At the presynapse, a variety of... (Review)
Review
The faithful formation and, consequently, function of a synapse requires continuous and tightly controlled delivery of synaptic material. At the presynapse, a variety of proteins with unequal molecular properties are indispensable to compose and control the molecular machinery concerting neurotransmitter release through synaptic vesicle fusion with the presynaptic membrane. As presynaptic proteins are produced mainly in the neuronal soma, they are obliged to traffic along microtubules through the axon to reach the consuming presynapse. This anterograde transport is performed by highly specialised and diverse presynaptic precursor vesicles, membranous organelles able to transport as different proteins such as synaptic vesicle membrane and membrane-associated proteins, cytosolic active zone proteins, ion-channels, and presynaptic membrane proteins, coordinating synaptic vesicle exo- and endocytosis. This review aims to summarise and categorise the diverse and numerous findings describing presynaptic precursor cargo, mode of trafficking, kinesin-based axonal transport and the molecular mechanisms of presynaptic precursor vesicles biogenesis in both vertebrate and invertebrate model systems.
PubMed: 37759474
DOI: 10.3390/cells12182248 -
Frontiers in Immunology 2020is the causative agent of a severe pneumonia called Legionnaires' disease. The environmental bacterium replicates in free-living amoebae as well as in lung macrophages... (Review)
Review
is the causative agent of a severe pneumonia called Legionnaires' disease. The environmental bacterium replicates in free-living amoebae as well as in lung macrophages in a distinct compartment, the -containing vacuole (LCV). The LCV communicates with a number of cellular vesicle trafficking pathways and is formed by a plethora of secreted bacterial effector proteins, which target host cell proteins and lipids. Phosphoinositide (PI) lipids are pivotal determinants of organelle identity, membrane dynamics and vesicle trafficking. Accordingly, eukaryotic cells tightly regulate the production, turnover, interconversion, and localization of PI lipids. modulates the PI pattern in infected cells for its own benefit by (i) recruiting PI-decorated vesicles, (ii) producing effectors acting as PI interactors, phosphatases, kinases or phospholipases, and (iii) subverting host PI metabolizing enzymes. The PI conversion from PtdIns(3) to PtdIns(4) represents a decisive step during LCV maturation. In this review, we summarize recent progress on elucidating the strategies, by which subverts host PI lipids to promote LCV formation and intracellular replication.
Topics: Bacterial Proteins; Cell Membrane; Endoplasmic Reticulum; Host-Pathogen Interactions; Humans; Legionella pneumophila; Legionnaires' Disease; Macrophages; Phosphatidylinositols; Secretory Vesicles; Transport Vesicles; Vacuoles
PubMed: 32117224
DOI: 10.3389/fimmu.2020.00025 -
Advances in Neurobiology 2023Neurotransmitters are stored in small membrane-bound vesicles at synapses; a subset of synaptic vesicles is docked at release sites. Fusion of docked vesicles with the...
Neurotransmitters are stored in small membrane-bound vesicles at synapses; a subset of synaptic vesicles is docked at release sites. Fusion of docked vesicles with the plasma membrane releases neurotransmitters. Membrane fusion at synapses, as well as all trafficking steps of the secretory pathway, is mediated by SNARE proteins. The SNAREs are the minimal fusion machinery. They zipper from N-termini to membrane-anchored C-termini to form a 4-helix bundle that forces the apposed membranes to fuse. At synapses, the SNAREs comprise a single helix from syntaxin and synaptobrevin; SNAP-25 contributes the other two helices to complete the bundle. Unc13 mediates synaptic vesicle docking and converts syntaxin into the permissive "open" configuration. The SM protein, Unc18, is required to initiate and proofread SNARE assembly. The SNAREs are then held in a half-zippered state by synaptotagmin and complexin. Calcium removes the synaptotagmin and complexin block, and the SNAREs drive vesicle fusion. After fusion, NSF and alpha-SNAP unwind the SNAREs and thereby recharge the system for further rounds of fusion. In this chapter, we will describe the discovery of the SNAREs, their relevant structural features, models for their function, and the central role of Unc18. In addition, we will touch upon the regulation of SNARE complex formation by Unc13, complexin, and synaptotagmin.
Topics: Humans; Membrane Fusion; SNARE Proteins; Synaptic Vesicles; Synaptic Transmission; Synaptotagmins
PubMed: 37615864
DOI: 10.1007/978-3-031-34229-5_4 -
Mass Spectrometry Reviews Mar 2023Extracellular vesicles from plasma, other body fluids and cell culture media hold great promise in the search for biomarkers. Exosomes in particular, the vesicle type... (Review)
Review
Extracellular vesicles from plasma, other body fluids and cell culture media hold great promise in the search for biomarkers. Exosomes in particular, the vesicle type that is secreted after being produced in the endocytic pathway and having a diameter of 30-150 nm, are considered to be a conveyance for signaling molecules and, therefore, to hold valuable information regarding the health and activity status of the cells from which they are released. The vesicular nature of exosomes is central to all methods used to separate them from the highly abundant proteins in plasma and other fluids. The enrichment of the vesicles is essential for mass spectrometry-based analysis as they represent only a very small component of all plasma proteins. The progression of isolation techniques for exosomes from ultracentrifugation through chromatographic separation using hydrophobic packing materials shows that effective enrichment is possible and that high throughput approaches to exosome enrichment are achievable.
Topics: Extracellular Vesicles; Ultracentrifugation; Exosomes; Mass Spectrometry; Blood Proteins
PubMed: 34632607
DOI: 10.1002/mas.21738 -
Advances in Experimental Medicine and... 2021Extracellular vesicles (EVs) are nano-sized, cell-released vesicles which contain lipids, proteins, and nucleic acids derived from the parental cells. EVs play an... (Review)
Review
Extracellular vesicles (EVs) are nano-sized, cell-released vesicles which contain lipids, proteins, and nucleic acids derived from the parental cells. EVs play an important role in intercellular communication and influence both physiological and pathological conditions. They are increasingly explored as potential therapeutic agents since they can cross biological barriers, their cargo is protected from degradation and they are involved in the transfer of bioactive components. EVs can promote tissue regeneration and might be alternatives to cell therapy. They can be used both in their native form, and as delivery vehicles for therapeutic agents. However, there are many hurdles to overcome for broad clinical application of EVs as therapeutics. Here, we review recent conditions regarding EVs therapeutics in regenerative medicine.
Topics: Cell Communication; Extracellular Vesicles; Nucleic Acids; Regenerative Medicine; Wound Healing
PubMed: 33330962
DOI: 10.1007/5584_2020_599 -
Annual Review of Analytical Chemistry... Jun 2020Neuronal transmission relies on electrical signals and the transfer of chemical signals from one neuron to another. Chemical messages are transmitted from presynaptic...
Neuronal transmission relies on electrical signals and the transfer of chemical signals from one neuron to another. Chemical messages are transmitted from presynaptic neurons to neighboring neurons through the triggered fusion of neurotransmitter-filled vesicles with the cell plasma membrane. This process, known as exocytosis, involves the rapid release of neurotransmitter solutions that are detected with high affinity by the postsynaptic neuron. The type and number of neurotransmitters released and the frequency of vesicular events govern brain functions such as cognition, decision making, learning, and memory. Therefore, to understand neurotransmitters and neuronal function, analytical tools capable of quantitative and chemically selective detection of neurotransmitters with high spatiotemporal resolution are needed. Electrochemistry offers powerful techniques that are sufficiently rapid to allow for the detection of exocytosis activity and provides quantitative measurements of vesicle neurotransmitter content and neurotransmitter release from individual vesicle events. In this review, we provide an overview of the most commonly used electrochemical methods for monitoring single-vesicle events, including recent developments and what is needed for future research.
PubMed: 32151142
DOI: 10.1146/annurev-anchem-061417-010032 -
Journal of Biosciences 2022Eukaryotic cells use small membrane-enclosed vesicles to transport molecular cargo between intracellular compartments. Interactions between molecules on vesicles and...
Eukaryotic cells use small membrane-enclosed vesicles to transport molecular cargo between intracellular compartments. Interactions between molecules on vesicles and compartments determine the source and target compartment of each vesicle type. The set of compartment and vesicle types in a cell define the nodes and edges of a transport graph known as the vesicle traffic network. The transmembrane SNARE proteins that regulate vesicle fusion to target compartments travel in cycles through the transport graph, but the paths they follow must be tightly regulated to avoid aberrant vesicle fusion. Here we use graph-theoretic ideas to understand how such molecular constraints place constraints on the structure of the transport graph. We identify edge connectivity (the minimum number of edges that must be removed to disconnect a graph) as a key determinant that separates allowed and disallowed types of transport graphs. As we increase the flexibility of molecular regulation, the required edge connectivity decreases, so more types of vesicle transport graphs are allowed. These results can be used to aid the discovery of new modes of molecular regulation and new vesicle traffic pathways.
Topics: Computational Biology; Computer Graphics; Eukaryotic Cells; SNARE Proteins; Transport Vesicles
PubMed: 35092413
DOI: No ID Found -
Cells, Tissues, Organs 2023Over the past 50 years, several different types of extracellular vesicles have been discovered including exosomes, microvesicles, and matrix vesicles. These vesicles are... (Review)
Review
Over the past 50 years, several different types of extracellular vesicles have been discovered including exosomes, microvesicles, and matrix vesicles. These vesicles are secreted by cells for specific purposes and contain cargo such as microRNA, cytokines, and lipids. A novel extracellular vesicle, the matrix-bound nanovesicle (MBV), has been recently discovered. The MBV is similar to the microvesicle, however, it is attached to the extracellular matrix, instead of being secreted. This review compares MBVs to other types of extracellular vesicles to try and better understand their origin and function. Further, this review will explain various extracellular vesicle isolation methods and how these can be used for MBVs and summarize characterization of MBV cargo such as microRNA, proteins, and lipids. Lastly, we will summarize the effects of MBVs on cells. MBVs are a novel class of extracellular vesicles that hold great promise as a platform for delivery of targeted gene and drug therapeutics.
Topics: Exosomes; Extracellular Vesicles; MicroRNAs; Proteins; Lipids
PubMed: 35168230
DOI: 10.1159/000522575 -
Journal of Nanobiotechnology Jan 2024With the immense progress in drug delivery systems (DDS) and the rise of nanotechnology, challenges such as target specificity remain. The vesicle-vector system (VVS) is... (Review)
Review
With the immense progress in drug delivery systems (DDS) and the rise of nanotechnology, challenges such as target specificity remain. The vesicle-vector system (VVS) is a delivery system that uses lipid-based vesicles as vectors for a targeted drug delivery. When modified with target-probing materials, these vesicles become powerful vectors for drug delivery with high target specificity. In this review, we discuss three general types of VVS based on different modification strategies: (1) vesicle-probes; (2) vesicle-vesicles; and (3) genetically engineered vesicles. The synthesis of each VVS type and their corresponding properties that are advantageous for targeted drug delivery, are also highlighted. The applications, challenges, and limitations of VVS are briefly examined. Finally, we share a number of insights and perspectives regarding the future of VVS as a targeted drug delivery system at the nanoscale.
Topics: Extracellular Vesicles; Drug Delivery Systems; Nanotechnology
PubMed: 38167116
DOI: 10.1186/s12951-023-02275-6 -
Neuroscience Nov 2022Depressive disorder is the leading cause of disability worldwide, yet the mechanisms underlying depression are not fully understood. Vesicle release is essential for... (Review)
Review
Depressive disorder is the leading cause of disability worldwide, yet the mechanisms underlying depression are not fully understood. Vesicle release is essential for synaptic neurotransmission, the abnormalities of vesicle release and synaptic plasticity are associated with various neuropsychiatric disorders. Neural circuits are ensembles of interconnected neurons that collectively perform specific functions. To some extent, depression may be caused by a disruption in the structural and functional connections of the neural circuits underlying emotion regulation. In this review, we summarized the role of abnormalities of vesicle release and synaptic transmission, as well as the related regulatory molecules and signal pathways in the regulation of depression.
Topics: Synaptic Vesicles; Depression; Synaptic Transmission; Neurons; Neuronal Plasticity; Synapses
PubMed: 36228829
DOI: 10.1016/j.neuroscience.2022.10.001