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Cellular and Molecular Life Sciences :... Sep 2008Vesicular transport is the basic communication mechanism between different compartments in a cell and with the environment. In this review I discuss the principles of... (Review)
Review
Vesicular transport is the basic communication mechanism between different compartments in a cell and with the environment. In this review I discuss the principles of vesicle generation and consumption with particular emphasis on the different types of coat proteins and the timing of the shedding of the coat proteins from transport containers. In recent years it has become clear that there are more coat complexes than the classical COPI, COPII and clathrin coats. These additional coats may generate vesicles that transport cargo in a temporally and/or spatially controlled manner. Work over the last years suggests that GTP hydrolysis occurs early during vesicle biogenesis, destabilizing the coat perhaps before fission of the vesicle from the donor membrane occurs. Recent findings imply, however, that tethers at the receiving compartment specifically detect the coat on vesicle.
Topics: ADP-Ribosylation Factors; Animals; Biological Transport; Cell Membrane; Coated Vesicles; Guanosine Triphosphate; Intracellular Membranes; SNARE Proteins; Transport Vesicles; Vesicular Transport Proteins
PubMed: 18726180
DOI: 10.1007/s00018-008-8349-y -
ACS Nano Jun 2022Release from nanobiovesicles via a pore generated by membrane electroporation at an electrified interface can be monitored by vesicle impact electrochemical cytometry...
Release from nanobiovesicles via a pore generated by membrane electroporation at an electrified interface can be monitored by vesicle impact electrochemical cytometry (VIEC) and provides rich information about the various vesicular content transfer processes, including content homeostasis, intraphase content transfer, or the transient fusion of vesicles. These processes are primarily influenced by the vesicular pore-opening dynamics at the electrified interface which has not been disclosed at the single nanobiovesicle level yet. In this work, after simultaneously measuring the size and release dynamics of individual vesicles, we employed a moving mesh-finite element simulation algorithm to reconstruct the accurate pore-opening dynamics of individual vesicles with different sizes during VIEC. We investigated the expansion times and maximal pore sizes as two characteristics of different vesicles. The pore expansion times between nanobiovesicles and pure lipid liposomes were compared, and that of the nanobiovesicles is much longer than that for the liposomes, 2.1 ms vs 0.18 ms, respectively, which reflects the membrane proteins limiting the electroporation process. For the vesicles with different sizes, a positive relationship of pore size () with the vesicle size () and also their ratio (/) versus the vesicle sizes is observed. The mechanism of the pore size determination is discussed and related to the membrane proteins and the vesicle size. This work accurately describes the dynamic pore-opening process of individual vesicles which discloses the heterogeneity in electroporation of different sized vesicles. This should allow us to examine the more complicated vesicular content transfer process between intravesicular compartments.
Topics: Liposomes; Electroporation; Computer Simulation; Membrane Proteins
PubMed: 35647887
DOI: 10.1021/acsnano.2c03929 -
Cancers Sep 2022Extracellular vesicles are membrane-bound vesicles released by cells to mediate intercellular communication and homeostasis. Various external stimuli as well as inherent... (Review)
Review
Extracellular vesicles are membrane-bound vesicles released by cells to mediate intercellular communication and homeostasis. Various external stimuli as well as inherent abnormalities result in alterations in the extracellular vesicle milieu. Changes to cells result in alterations in the content of the extracellular vesicle biogenesis, which may affect proximal and distal cells encountering these altered extracellular vesicles. Therefore, the examination of changes in the extracellular vesicle signature can be used to follow disease progression, reveal possible targets to improve therapy, as well as to serve as mediators of therapy. Furthermore, recent studies have developed methods to alter the cargo of extracellular vesicles to restore normal function or deliver therapeutic agents. This review will examine how extracellular vesicles from cancer cells differ from normal cells, how these altered extracellular vesicles can contribute to cancer progression, and how extracellular vesicles can be used as a therapeutic agent to target cancer cells and cancer-associated stroma. Here we present extracellular vesicles as a novel tool in nanomedicine.
PubMed: 36139610
DOI: 10.3390/cancers14184450 -
Journal of Structural Biology Oct 2016Macro-autophagy (autophagy) is a conserved catabolic pathway for the degradation of cytoplasmic material in the lysosomal system. This is achieved by the sequestration... (Review)
Review
Macro-autophagy (autophagy) is a conserved catabolic pathway for the degradation of cytoplasmic material in the lysosomal system. This is achieved by the sequestration of the cytoplasmic cargo material within double membrane-bound vesicles that fuse with lysosomes, wherein the vesicle's inner membrane and the cargo are degraded. Autophagosomes form in a de novo manner and their precursors are initially detected as small membrane structures that are referred to as isolation membranes. The isolation membranes gradually expand and subsequently close to give rise to autophagosomes. Many proteins required to form autophagosomes have been identified but how they act mechanistically is still enigmatic. Here we critically review reconstitution approaches employed to decipher the inner working of the fascinating autophagy machinery.
Topics: Animals; Autophagosomes; Humans; Membranes; Organelle Biogenesis; Proteins
PubMed: 27251905
DOI: 10.1016/j.jsb.2016.04.005 -
Neuron Jul 2006The question of how synapses maintain an active recycling pool of synaptic vesicles to support high-frequency synaptic transmission has been a perplexing and often... (Review)
Review
The question of how synapses maintain an active recycling pool of synaptic vesicles to support high-frequency synaptic transmission has been a perplexing and often controversial problem. In this issue of Neuron, Fernandez-Alfonso et al. present data indicating that at least two synaptic vesicle proteins, synaptotagmin 1 and VAMP-2, are present in a large pool on the synaptic and axonal plasma membrane and can interchange with recently exocytosed proteins. These findings suggest that a plasma membrane pool of synaptic vesicle proteins provides a reservoir that can facilitate rapid endocytosis.
Topics: Animals; Endocytosis; Humans; Models, Neurological; Synaptic Vesicles
PubMed: 16846848
DOI: 10.1016/j.neuron.2006.07.002 -
Environmental Research Mar 2022A relationship between environmental exposure to air pollution and cognitive impairment and neurological disorders has been described. Previous literature has focused on... (Review)
Review
A relationship between environmental exposure to air pollution and cognitive impairment and neurological disorders has been described. Previous literature has focused on the direct effects of the air pollution components on neuronal and glial cells, as well as on involvement of oxidative stress and neuroinflammation on microglia and astrocyte reactivity. However, other mechanisms involved in the air pollution effects on central nervous system (CNS) toxicity can be playing critical roles. Increasingly, extracellular vesicle's (EVs) mediated intercellular communication is being recognized as impacting the development of cognitive impairment and neurological disorders like Alzheimer's disease and others. Here we describe the available evidence about toxic air pollutants and its components on brain, an involvement of brain cells specific and EVs types (based in the origin or in the size of EVs) in the initiation, exacerbation, and propagation of the neurotoxic effects (inflammation, neurodegeneration, and accumulation of neurotoxic proteins) induced by air pollution in the CNS. Additionally, we discuss the identification and isolation of neural-derived EVs from human plasma, the most common markers for neural-derived EVs, and their potential for use as diagnostic or therapeutic molecules for air pollution-related cognitive impairment and neurodegeneration.
Topics: Air Pollution; Alzheimer Disease; Brain; Cognitive Dysfunction; Extracellular Vesicles; Humans
PubMed: 34728237
DOI: 10.1016/j.envres.2021.112316 -
The Journal of Neuroscience : the... Dec 2022The statistics of vesicle release determine how synapses transfer information, but the classical Poisson model of independent release does not always hold at the first...
The statistics of vesicle release determine how synapses transfer information, but the classical Poisson model of independent release does not always hold at the first stages of vision and hearing. There, ribbon synapses also encode sensory signals as events comprising two or more vesicles released simultaneously. The implications of such coordinated multivesicular release (MVR) for spike generation are not known. Here we investigate how MVR alters the transmission of sensory information compared with Poisson synapses using a pure rate-code. We used leaky integrate-and-fire models incorporating the statistics of release measured experimentally from glutamatergic synapses of retinal bipolar cells in zebrafish (both sexes) and compared these with models assuming Poisson inputs constrained to operate at the same average rates. We find that MVR can increase the number of spikes generated per vesicle while reducing interspike intervals and latency to first spike. The combined effect was to increase the efficiency of information transfer (bits per vesicle) over a range of conditions mimicking target neurons of different size. MVR was most advantageous in neurons with short time constants and reliable synaptic inputs, when less convergence was required to trigger spikes. In the special case of a single input driving a neuron, as occurs in the auditory system of mammals, MVR increased information transfer whenever spike generation required more than one vesicle. This study demonstrates how presynaptic integration of vesicles by MVR can increase the efficiency with which sensory information is transmitted compared with a rate-code described by Poisson statistics. Neurons communicate by the stochastic release of vesicles at the synapse and the statistics of this process will determine how information is represented by spikes. The classical model is that vesicles are released independently by a Poisson process, but this does not hold at ribbon-type synapses specialized to transmit the first electrical signals in vision and hearing, where two or more vesicles can fuse in a single event by a process termed coordinated multivesicular release. This study shows that multivesicular release can increase the number of spikes generated per vesicle and the efficiency of information transfer (bits per vesicle) over a range of conditions found in the retina and peripheral auditory system.
Topics: Male; Animals; Female; Synaptic Vesicles; Zebrafish; Synapses; Retinal Bipolar Cells; Retina; Synaptic Transmission; Mammals
PubMed: 36344266
DOI: 10.1523/JNEUROSCI.0717-22.2022 -
The Journal of Neuroscience : the... Feb 2021The BAD-BAX-caspase-3 cascade is a canonical apoptosis pathway. Macroautophagy ("autophagy" hereinafter) is a process by which organelles and aggregated proteins are...
The BAD-BAX-caspase-3 cascade is a canonical apoptosis pathway. Macroautophagy ("autophagy" hereinafter) is a process by which organelles and aggregated proteins are delivered to lysosomes for degradation. Here, we report a new function of the BAD-BAX-caspase-3 cascade and autophagy in the control of synaptic vesicle pools. We found that, in hippocampal neurons of male mice, the BAD-BAX-caspase-3 pathway regulates autophagy, which in turn limits the size of synaptic vesicle pools and influences the kinetics of activity-induced depletion and recovery of synaptic vesicle pools. Moreover, the caspase-autophagy pathway is engaged by fear conditioning to facilitate associative fear learning and memory. This work identifies a new mechanism for controlling synaptic vesicle pools, and a novel, nonapoptotic, presynaptic function of the BAD-BAX-caspase-3 cascade. Despite the importance of synaptic vesicles for neurons, little is known about how the size of synaptic vesicle pools is maintained under basal conditions and regulated by neural activity. This study identifies a new mechanism for the control of synaptic vesicle pools, and a new, nonapoptotic function of the BAD-BAX-caspase-3 pathway in presynaptic terminals. Additionally, it indicates that autophagy is not only a homeostatic mechanism to maintain the integrity of cells and tissues, but also a process engaged by neural activity to regulate synaptic vesicle pools for optimal synaptic responses, learning, and memory.
Topics: Animals; Autophagy; Caspase 3; Cells, Cultured; HEK293 Cells; Humans; Male; Mice; Mice, Knockout; Molecular Imaging; Organ Culture Techniques; Signal Transduction; Synaptic Vesicles; bcl-2-Associated X Protein; bcl-Associated Death Protein
PubMed: 33303681
DOI: 10.1523/JNEUROSCI.0969-20.2020 -
Toxicon : Official Journal of the... Oct 2009Botulinum neurotoxins (BoNTs) elicit flaccid paralysis by cleaving SNARE proteins within peripheral neurons. BoNTs are classified into seven serotypes, termed A-G, based... (Review)
Review
Botulinum neurotoxins (BoNTs) elicit flaccid paralysis by cleaving SNARE proteins within peripheral neurons. BoNTs are classified into seven serotypes, termed A-G, based on antibody cross-neutralization. Clostridia produce BoNTs as single-chain toxins that are cleaved into a di-chain protein that comprises an N-terminal zinc metalloprotease domain that is linked by a disulfide bond to the C-terminal translocation/receptor-binding domain. BoNT/A and BoNT/B utilize synaptic vesicle protein 2 (SV2) and synaptotagmin, respectively, as receptors for entry into neurons. Using affinity chromatography, BoNT/A and BoNT/B were found to bind a synaptic vesicle protein complex in CHAPS extracts of synaptic vesicles. Mass spectroscopy identified synaptic vesicle protein 2, synaptotagmin I, synaptophysin, vesicle-associated membrane protein 2, and the vacuolar ATPase-proton pump as components of the BoNT-synaptic vesicle protein complex. BoNT/A and BoNT/B possessed unique density-gradient profiles when bound to synaptic vesicle protein complexes. The identification of BoNT/A and BoNT/B bound to synaptic vesicle protein complexes provides insight into the interactions of BoNT and neuronal receptors.
Topics: Animals; Botulinum Toxins; Humans; Membrane Glycoproteins; Nerve Tissue Proteins; Neurotoxins; Protein Binding; SNARE Proteins; Structure-Activity Relationship; Synaptic Vesicles
PubMed: 19362106
DOI: 10.1016/j.toxicon.2009.01.040 -
Frontiers in Synaptic Neuroscience 2010The assembly of SNARE complexes between syntaxin, SNAP-25 and synaptobrevin is required to prime synaptic vesicles for fusion. Since Munc18 and tomosyn compete for...
The assembly of SNARE complexes between syntaxin, SNAP-25 and synaptobrevin is required to prime synaptic vesicles for fusion. Since Munc18 and tomosyn compete for syntaxin interactions, the interplay between these proteins is predicted to be important in regulating synaptic transmission. We explored this possibility, by examining genetic interactions between C. elegans unc-18(Munc18), unc-64(syntaxin) and tom-1(tomosyn). We have previously demonstrated that unc-18 mutants have reduced synaptic transmission, whereas tom-1 mutants exhibit enhanced release. Here we show that the unc-18 mutant release defect is associated with loss of two morphologically distinct vesicle pools; those tethered within 25 nm of the plasma membrane and those docked with the plasma membrane. In contrast, priming defective unc-13 mutants accumulate tethered vesicles, while docked vesicles are greatly reduced, indicating tethering is UNC-18-dependent and occurs in the absence of priming. C. elegans unc-64 mutants phenocopy unc-18 mutants, losing both tethered and docked vesicles, whereas overexpression of open syntaxin preferentially increases vesicle docking, suggesting UNC-18/closed syntaxin interactions are responsible for vesicle tethering. Given the competition between vertebrate tomosyn and Munc18, for syntaxin binding, we hypothesized that C. elegans TOM-1 may inhibit both UNC-18-dependent vesicle targeting steps. Consistent with this hypothesis, tom-1 mutants exhibit enhanced UNC-18 plasma membrane localization and a concomitant increase in both tethered and docked synaptic vesicles. Furthermore, in tom-1;unc-18 double mutants the docked, primed vesicle pool is preferentially rescued relative to unc-18 single mutants. Together these data provide evidence for the differential regulation of two vesicle targeting steps by UNC-18 and TOM-1 through competitive interactions with syntaxin.
PubMed: 21423527
DOI: 10.3389/fnsyn.2010.00141