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The Biochemical Journal Feb 2022Membrane traffic in eukaryotic cells is mediated by transport vesicles that bud from a precursor compartment and are transported to their destination compartment where... (Review)
Review
Membrane traffic in eukaryotic cells is mediated by transport vesicles that bud from a precursor compartment and are transported to their destination compartment where they dock and fuse. To reach their intracellular destination, transport vesicles contain targeting signals such as Rab GTPases and polyphosphoinositides that are recognized by tethering factors in the cytoplasm and that connect the vesicles with their respective destination compartment. The final step, membrane fusion, is mediated by SNARE proteins. SNAREs are connected to targeting signals and tethering factors by multiple interactions. However, it is still debated whether SNAREs only function downstream of targeting and tethering or whether they also participate in regulating targeting specificity. Here, we review the evidence and discuss recent data supporting a role of SNARE proteins as targeting signals in vesicle traffic.
Topics: Cell Membrane; Eukaryotic Cells; Humans; Membrane Fusion; Protein Transport; SNARE Proteins; Signal Transduction; Transport Vesicles; rab GTP-Binding Proteins
PubMed: 35119456
DOI: 10.1042/BCJ20210719 -
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 -
International Journal of Biological... 2024The mechanism that maintains ER-to-Golgi vesicles formation and transport is complicated. As one of the adapters, Ninein-like protein (Nlp) participated in assembly and... (Review)
Review
The mechanism that maintains ER-to-Golgi vesicles formation and transport is complicated. As one of the adapters, Ninein-like protein (Nlp) participated in assembly and transporting of partial ER-to-Golgi vesicles that contained specific proteins, such as β-Catenin and STING. Nlp acted as a platform to sustain the specificity and continuity of cargoes during COPII and COPI-coated vesicle transition and transportation through binding directly with SEC31A as well as Rab1B. Thus, we proposed an integrated transport model that particular adapter participated in specific cargo selection or transportation through cooperating with different membrane associated proteins to ensure the continuity of cargo trafficking. Deficiency of Nlp led to vesicle budding failure and accumulation of unprocessed proteins in ER, which further caused ER stress as well as Golgi fragmentation, and PERK-eIF2α pathway of UPR was activated to reduce the synthesis of universal proteins. In contrast, upregulation of Nlp resulted in Golgi fragmentation, which enhanced the cargo transport efficiency between ER and Golgi. Moreover, deficient mice were prone to spontaneous B cell lymphoma, since the developments and functions of lymphocytes significantly depended on secretory proteins through ER-to-Golgi vesicle trafficking, including IL-13, IL-17 and IL-21. Thus, perturbations of Nlp altered ER-to-Golgi communication and cellular homeostasis, and might contribute to the pathogenesis of B cell lymphoma.
Topics: Endoplasmic Reticulum; Animals; Golgi Apparatus; Humans; Mice; Protein Transport; COP-Coated Vesicles
PubMed: 38904019
DOI: 10.7150/ijbs.91792 -
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 -
Vaccines Sep 2023Extracellular vesicles (EVs) are lipid membrane-enclosed particles produced by most cells, playing important roles in various biological processes. They have been shown... (Review)
Review
Extracellular vesicles (EVs) are lipid membrane-enclosed particles produced by most cells, playing important roles in various biological processes. They have been shown to be involved in antiviral mechanisms such as transporting antiviral molecules, transmitting viral resistance, and participating in antigen presentation. While viral transmission was traditionally thought to occur through independent viral particles, the process of viral infection is complex, with multiple barriers and challenges that viruses must overcome for successful infection. As a result, viruses exploit the intercellular communication pathways of EVs to facilitate cluster transmission, increasing their chances of infecting target cells. Viral vesicle transmission offers two significant advantages. Firstly, it enables the collective transmission of viral genomes, increasing the chances of infection and promoting interactions between viruses in subsequent generations. Secondly, the use of vesicles as vehicles for viral transmission provides protection to viral particles against environmental factors, while also expanding the cell tropism allowing viruses to reach cells in a receptor-independent manner. Understanding the role of EVs in viral transmission is crucial for comprehending virus evolution and developing innovative antiviral strategies, therapeutic interventions, and vaccine approaches.
PubMed: 37896936
DOI: 10.3390/vaccines11101532 -
Journal of Structural Biology Mar 2022Protein transport between the membranous compartments of the eukaryotic cells is mediated by the constant fission and fusion of the membrane-bounded vesicles from a... (Review)
Review
Protein transport between the membranous compartments of the eukaryotic cells is mediated by the constant fission and fusion of the membrane-bounded vesicles from a donor to an acceptor membrane. While there are many membrane remodelling complexes in eukaryotes, COPII, COPI, and clathrin-coated vesicles are the three principal classes of coat protein complexes that participate in vesicle trafficking in the endocytic and secretory pathways. These vesicle-coat proteins perform two key functions: deforming lipid bilayers into vesicles and encasing selective cargoes. The three trafficking complexes share some commonalities in their structural features but differ in their coat structures, mechanisms of cargo sorting, vesicle formation, and scission. While the structures of many of the proteins involved in vesicle formation have been determined in isolation by X-ray crystallography, elucidating the proteins' structures together with the membrane is better suited for cryogenic electron microscopy (cryo-EM). In recent years, advances in cryo-EM have led to solving the structures and mechanisms of several vesicle trafficking complexes and associated proteins.
Topics: Coat Protein Complex I; Cryoelectron Microscopy; Crystallography, X-Ray; Membranes; Protein Transport
PubMed: 35101600
DOI: 10.1016/j.jsb.2022.107836 -
Cell Calcium Jan 2022In some lysosomal storage diseases (LSD) cholesterol accumulates in vesicles. Whether increased vesicle cholesterol affects vesicle fusion with the plasmalemma, where...
In some lysosomal storage diseases (LSD) cholesterol accumulates in vesicles. Whether increased vesicle cholesterol affects vesicle fusion with the plasmalemma, where the fusion pore, a channel between the vesicle lumen and the extracellular space, is formed, is unknown. Super-resolution microscopy revealed that after stimulation of exocytosis, pituitary lactotroph vesicles discharge cholesterol which transfers to the plasmalemma. Cholesterol depletion in lactotrophs and astrocytes, both exhibiting Ca-dependent exocytosis regulated by distinct Casources, evokes vesicle secretion. Although this treatment enhanced cytosolic levels of Ca in lactotrophs but decreased it in astrocytes, this indicates that cholesterol may well directly define the fusion pore. In an attempt to explain this mechanism, a new model of cholesterol-dependent fusion pore regulation is proposed. High-resolution membrane capacitance measurements, used to monitor fusion pore conductance, a parameter related to fusion pore diameter, confirm that at resting conditions reducing cholesterol increases, while enrichment with cholesterol decreases the conductance of the fusion pore. In resting fibroblasts, lacking the Npc1 protein, a cellular model of LSD in which cholesterol accumulates in vesicles, the fusion pore conductance is smaller than in controls, showing that vesicle cholesterol controls fusion pore and is relevant for pathophysiology of LSD.
Topics: Animals; Cell Membrane; Cholesterol; Exocytosis; Lactotrophs; Membrane Fusion; Rats; Rats, Wistar; Secretory Vesicles
PubMed: 34844123
DOI: 10.1016/j.ceca.2021.102503 -
Journal of Neurochemistry Apr 2021Parkinson's disease is a common neurodegenerative disorder and is clinically characterized by bradykinesia, rigidity, and resting tremor. Missense mutations in the... (Review)
Review
Parkinson's disease is a common neurodegenerative disorder and is clinically characterized by bradykinesia, rigidity, and resting tremor. Missense mutations in the leucine-rich repeat protein kinase-2 gene (LRRK2) are a recognized cause of inherited Parkinson's disease. The physiological and pathological impact of LRRK2 is still obscure, but accumulating evidence indicates that LRRK2 orchestrates diverse aspects of membrane trafficking, such as membrane fusion and vesicle formation and transport along actin and tubulin tracks. In the present review, we focus on the special relation between LRRK2 and synaptic vesicles. LRRK2 binds and phosphorylates key actors within the synaptic vesicle cycle. Accordingly, alterations in dopamine and glutamate transmission have been described upon LRRK2 manipulations. However, the different modeling strategies and phenotypes observed require a critical approach to decipher the outcome of LRRK2 at the pre-synaptic site.
Topics: Animals; Endocytosis; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Neurons; Parkinson Disease; Presynaptic Terminals; Synaptic Vesicles
PubMed: 33206398
DOI: 10.1111/jnc.15240 -
Extreme Mechanics Letters Feb 2021The physico-mechanical properties of nanoscale lipid vesicles (e.g., natural nano-vesicles and artificial nano-liposomes) dictate their interaction with biological...
The physico-mechanical properties of nanoscale lipid vesicles (e.g., natural nano-vesicles and artificial nano-liposomes) dictate their interaction with biological systems. Understanding the interplay between vesicle size and stiffness is critical to both the understanding of the biological functions of natural nano-vesicles and the optimization of nano-vesicle-based diagnostics and therapeutics. It has been predicted that, when vesicle size is comparable to its membrane thickness, the effective bending stiffness of the vesicle increases dramatically due to both the entropic effect as a result of reduced thermal undulation and the nonlinear curvature elasticity effect. Through systematic molecular dynamics simulations, we show that the vesicle membrane thins and softens with the decrease in vesicle size, which effectively counteracts the stiffening effects as already mentioned. Our simulations indicate that the softening of nano-vesicles results from a change in the bilayer's interior structure - a decrease in lipid packing order - as the membrane curvature increases. Our work thus leads to a more complete physical framework to understand the physico-mechanical properties of nanoscale lipid vesicles, paving the way to further advances in the biophysics of nano-vesicles and their biomedical applications.
PubMed: 33542946
DOI: 10.1016/j.eml.2021.101174