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Cell Communication and Signaling : CCS Aug 2023Traumatic brain injury (TBI) is a leading cause of injury-related disability and death around the world, but the clinical stratification, diagnosis, and treatment of... (Review)
Review
Traumatic brain injury (TBI) is a leading cause of injury-related disability and death around the world, but the clinical stratification, diagnosis, and treatment of complex TBI are limited. Due to their unique properties, extracellular vesicles (EVs) are emerging candidates for being biomarkers of traumatic brain injury as well as serving as potential therapeutic targets. However, the effects of different extracellular vesicle subtypes on the pathophysiology of traumatic brain injury are very different, or potentially even opposite. Before extracellular vesicles can be used as targets for TBI therapy, it is necessary to classify different extracellular vesicle subtypes according to their functions to clarify different strategies for EV-based TBI therapy. The purpose of this review is to discuss contradictory effects of different EV subtypes on TBI, and to propose treatment ideas based on different EV subtypes to maximize their benefits for the recovery of TBI patients. Video Abstract.
Topics: Humans; Brain Injuries, Traumatic; Extracellular Vesicles
PubMed: 37596642
DOI: 10.1186/s12964-023-01165-6 -
Molecules (Basel, Switzerland) Mar 2023The vesicle mechanical behaviors were studied upon its exposure to 3-hydroxybutyric acid using an atomic force microscope (AFM). Dipalmitoylphosphatidylcholine (DPPC)...
The vesicle mechanical behaviors were studied upon its exposure to 3-hydroxybutyric acid using an atomic force microscope (AFM). Dipalmitoylphosphatidylcholine (DPPC) and 3-hydroxybutyric acid were used to manufacture the vesicles at their desired ratio. The deflection of an AFM probe with respect to its displacement was measured after characterizing the vesicle adsorption. The movement was analyzed with the Hertzian model to understand the physical behavior of the vesicles. However, in the deflection just prior to the first penetration, the model was a good fit, and the vesicle mechanical moduli were calculated. The moduli became lower with the higher ratio of 3-hydroxybutyric acid to DPPC, but the moduli were saturated at 0.5 of the ratio. These results appear to be the basis for the function of the metabolism associated with 3-hydroxybutyric acid, i.e., anesthetization and glycemic control, on the physical properties of cell membranes.
Topics: 3-Hydroxybutyric Acid; Microscopy, Atomic Force; 1,2-Dipalmitoylphosphatidylcholine; Adsorption
PubMed: 36985713
DOI: 10.3390/molecules28062742 -
Philosophical Transactions of the Royal... Mar 2021Neurosecretory vesicles are highly specialized trafficking organelles that store neurotransmitters that are released at presynaptic nerve endings and are, therefore,...
Neurosecretory vesicles are highly specialized trafficking organelles that store neurotransmitters that are released at presynaptic nerve endings and are, therefore, important for animal cell-cell signalling. Despite considerable anatomical and functional diversity of neurons in animals, the protein composition of neurosecretory vesicles in bilaterians appears to be similar. This similarity points towards a common evolutionary origin. Moreover, many putative homologues of key neurosecretory vesicle proteins predate the origin of the first neurons, and some even the origin of the first animals. However, little is known about the molecular toolkit of these vesicles in non-bilaterian animals and their closest unicellular relatives, making inferences about the evolutionary origin of neurosecretory vesicles extremely difficult. By comparing 28 proteins of the core neurosecretory vesicle proteome in 13 different species, we demonstrate that most of the proteins are present in unicellular organisms. Surprisingly, we find that the vesicular membrane-associated soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein synaptobrevin is localized to the vesicle-rich apical and basal pole in the choanoflagellate Our 3D vesicle reconstructions reveal that the choanoflagellates and exhibit a polarized and diverse vesicular landscape reminiscent of the polarized organization of chemical synapses that secrete the content of neurosecretory vesicles into the synaptic cleft. This study sheds light on the ancestral molecular machinery of neurosecretory vesicles and provides a framework to understand the origin and evolution of secretory cells, synapses and neurons. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.
Topics: Biological Evolution; Choanoflagellata; R-SNARE Proteins; Synaptic Vesicles
PubMed: 33550951
DOI: 10.1098/rstb.2019.0759 -
Cells Apr 2023Connexin 43, an astroglial gap junction protein, is enriched in perisynaptic astroglial processes and plays major roles in synaptic transmission. We have previously...
Connexin 43, an astroglial gap junction protein, is enriched in perisynaptic astroglial processes and plays major roles in synaptic transmission. We have previously found that astroglial Cx43 controls synaptic glutamate levels and allows for activity-dependent glutamine release to sustain physiological synaptic transmissions and cognitiogns. However, whether Cx43 is important for the release of synaptic vesicles, which is a critical component of synaptic efficacy, remains unanswered. Here, using transgenic mice with a glial conditional knockout of Cx43 (Cx43-/-), we investigate whether and how astrocytes regulate the release of synaptic vesicles from hippocampal synapses. We report that CA1 pyramidal neurons and their synapses develop normally in the absence of astroglial Cx43. However, a significant impairment in synaptic vesicle distribution and release dynamics were observed. In particular, the FM1-43 assays performed using two-photon live imaging and combined with multi-electrode array stimulation in acute hippocampal slices, revealed a slower rate of synaptic vesicle release in Cx43-/- mice. Furthermore, paired-pulse recordings showed that synaptic vesicle release probability was also reduced and is dependent on glutamine supply via Cx43 hemichannel (HC). Taken together, we have uncovered a role for Cx43 in regulating presynaptic functions by controlling the rate and probability of synaptic vesicle release. Our findings further highlight the significance of astroglial Cx43 in synaptic transmission and efficacy.
Topics: Mice; Animals; Connexin 43; Synaptic Vesicles; Astrocytes; Glutamine; Synapses; Hippocampus; Mice, Transgenic
PubMed: 37190042
DOI: 10.3390/cells12081133 -
Journal of Pharmacy & Pharmaceutical... 2021Neurons are special polarized cells whose synaptic vesicles release neurotransmitters into the synaptic cleft, acting on postsynaptic receptors and thus transmitting... (Review)
Review
Neurons are special polarized cells whose synaptic vesicles release neurotransmitters into the synaptic cleft, acting on postsynaptic receptors and thus transmitting information from presynaptic to postsynaptic states. The integrity of the vesicle cycle is critical to the transmission of neural signals in the brain. According to the molecular mechanism of calcium-triggered release, the assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) is required in the process of synaptic vesicle fusion and vesicle exocytosis. Many delicate steps are required to maintain the dynamic process of 'release-recycle', including intermediate processes and the dynamic balance of neurotransmission. Various neurodegenerative and neuropsychiatric diseases result from synaptic cycle dysfunction. This review of the relationships between the structure and function of synaptic vesicles in physiological and pathological conditions provides a theoretical basis for synaptic transmission and a novel avenue for the study of synaptic plasticity associated with mood disorders, highlighting potential targets for treating diseases.
Topics: Animals; Calcium; Exocytosis; Humans; Nervous System Diseases; Neuronal Plasticity; Neurons; Synapses; Synaptic Transmission; Synaptic Vesicles
PubMed: 34343470
DOI: 10.18433/jpps31458 -
Frontiers in Microbiology 2021Bacterial membrane vesicles (MVs) are produced by both Gram-positive and Gram-negative bacteria during growth and . MVs are nanoscale vesicular structures with... (Review)
Review
Bacterial membrane vesicles (MVs) are produced by both Gram-positive and Gram-negative bacteria during growth and . MVs are nanoscale vesicular structures with diameters ranging from 20 to 400 nm. MVs incorporate bacterial lipids, proteins, and often nucleic acids, and can effectively stimulate host immune response against bacterial infections. As vaccine candidates and drug delivery systems, MVs possess high biosafety owing to the lack of self-replication ability. However, wild-type bacterial strains have poor MV yield, and MVs from the wild-type strains may be harmful due to the carriage of toxic components, such as lipopolysaccharides, hemolysins, enzymes, etc. In this review, we summarize the genetic modification of vesicle-producing bacteria to reduce MV toxicity, enhance vesicle immunogenicity, and increase vesicle production. The engineered MVs exhibit broad applications in vaccine designs, vaccine delivery vesicles, and drug delivery systems.
PubMed: 34690971
DOI: 10.3389/fmicb.2021.729369 -
Biophysics Reports Apr 2021The transport of cargo proteins to specific subcellular destinations is crucial for the different secretory and endocytic traffic pathways. One of the most important...
The transport of cargo proteins to specific subcellular destinations is crucial for the different secretory and endocytic traffic pathways. One of the most important steps in maintaining the accuracy of this process is the recruitment of adaptor protein (AP) complexes to the membrane for recognizing and packaging cargo proteins into nascent vesicles. Adaptor protein complex 3 (AP-3) is a heterotetrametric complex implicated in the trafficking of cargo proteins from the trans-Golgi network (TGN) and/or endosomes to lysosomes or lysosome-related organelles (LROs). This complex is also involved in the biogenesis of synaptic vesicles (SVs) in neurons and of dense core vesicles (DCVs) in endocrine cells as well as in the recycling of receptors in immune cells and the regulation of planar cell polarity (PCP) proteins. Functional defects in AP-3 cause multiple abnormalities in cellular vesicle trafficking and related organelle function, leading to various disorders, such as Hermansky-Pudlak syndrome (HPS). However, the molecular mechanism underlying AP-3 has not been fully elucidated, and further investigations are needed to understand AP-3-mediated trafficking, its associated molecules and its related roles in inherited diseases. Here, we review the current understanding of AP-3 in cellular vesicle trafficking, especially focusing on mammalian systems.
PubMed: 37288146
DOI: 10.52601/bpr.2021.200051 -
Environmental Science & Technology Jun 2022Recent discovery of vesicle-cloaked virus clusters (i.e., viral vesicles) has greatly challenged the central paradigm of viral transmission and infection as a single...
Recent discovery of vesicle-cloaked virus clusters (i.e., viral vesicles) has greatly challenged the central paradigm of viral transmission and infection as a single virion. To understand the environmental transmission of viral vesicles, we used an in vivo model to investigate their environmental persistence and engineering control by disinfection. Murine rotavirus vesicles maintained both their integrity and infectivity after incubation in filtered freshwater and wastewater for at least 7 days, with 24.5-27.5% of the vesicles still intact at 16 weeks after exposure to both waters. Free chlorine disinfection at a dosage of 13.3 mg min L did not decompose murine rotavirus vesicles, and it was much less effective in inactivating rotaviruses inside vesicles than free rotaviruses based on the quantification of rotavirus shedding in mouse stool and rotavirus replication in small intestines. Rotavirus vesicles may be more environmentally transmissible than free rotaviruses regardless of disinfection. Vesicle-mediated transmission could be responsible for vesicles' resistance to disinfection due to an increased multiplicity of infection and/or genetic recombination or reassortment to promote infection. Our work highlights the environmental, biological, and public health significance of viral vesicles, and the findings call for urgent action in advancing disinfection for pathogen control.
Topics: Animals; Chlorine; Disinfection; Feces; Mice; Rotavirus; Wastewater
PubMed: 35653550
DOI: 10.1021/acs.est.2c00732 -
The EMBO Journal Nov 2021All bacteria produce secreted vesicles that carry out a variety of important biological functions. These extracellular vesicles can improve adaptation and survival by... (Review)
Review
All bacteria produce secreted vesicles that carry out a variety of important biological functions. These extracellular vesicles can improve adaptation and survival by relieving bacterial stress and eliminating toxic compounds, as well as by facilitating membrane remodeling and ameliorating inhospitable environments. However, vesicle production comes with a price. It is energetically costly and, in the case of colonizing pathogens, it elicits host immune responses, which reduce bacterial viability. This raises an interesting paradox regarding why bacteria produce vesicles and begs the question as to whether the benefits of producing vesicles outweigh their costs. In this review, we discuss the various advantages and disadvantages associated with Gram-negative and Gram-positive bacterial vesicle production and offer perspective on the ultimate score. We also highlight questions needed to advance the field in determining the role for vesicles in bacterial survival, interkingdom communication, and virulence.
Topics: Animals; Extracellular Vesicles; Gene Expression; Gram-Negative Bacteria; Gram-Positive Bacteria; Host-Parasite Interactions; Humans; Immunity, Innate; Microbial Viability; Quorum Sensing; Secretory Vesicles; Virulence; Virulence Factors
PubMed: 34636061
DOI: 10.15252/embj.2021108174 -
BioRxiv : the Preprint Server For... Jul 2023VPS50, is an accessory protein, involved in the synaptic and dense core vesicle acidification and its alterations produce behavioral changes in C.elegans. Here, we...
VPS50, is an accessory protein, involved in the synaptic and dense core vesicle acidification and its alterations produce behavioral changes in C.elegans. Here, we produce the mosaic knock out (mKO) of VPS50 using CRISPR/Cas9 system in both cortical cultured neurons and whole animals to evaluate the effect of VPS50 in regulating mammalian brain function and behavior. While mKO of VPS50 does not change the number of synaptic vesicles, it produces a mislocalization of the V-ATPase pump that likely impact in vesicle acidification and vesicle content to impair synaptic and neuronal activity in cultured neurons. In mice, mKO of VPS50 in the hippocampus, alter synaptic transmission and plasticity, and generated robust cognitive impairments associate to memory formation. We propose that VPS50 is an accessory protein that aids the correct recruitment of the V-ATPase pump to synaptic vesicles, thus having a crucial role controlling synaptic vesicle acidification and hence synaptic transmission.
PubMed: 37461727
DOI: 10.1101/2023.07.04.547745