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Neuroscience Jan 2009Expression of the integral and associated proteins of synaptic vesicles is subject to regulation over time, by region, and in response to activity. The process by which... (Review)
Review
Expression of the integral and associated proteins of synaptic vesicles is subject to regulation over time, by region, and in response to activity. The process by which changes in protein levels and isoforms result in different properties of neurotransmitter release involves protein trafficking to the synaptic vesicle. How newly synthesized proteins are incorporated into synaptic vesicles at the presynaptic bouton is poorly understood. During synaptogenesis, synaptic vesicle proteins sort through the secretory pathway and are transported down the axon in precursor vesicles that undergo maturation to form synaptic vesicles. Changes in protein content of synaptic vesicles could involve the formation of new vesicles that either mix with the previous complement of vesicles or replace them, presumably by their degradation or inactivation. Alternatively, new proteins could individually incorporate into existing synaptic vesicles, changing their functional properties. Glutamatergic vesicles likely express many of the same integral membrane proteins and share certain common mechanisms of biogenesis, recycling, and degradation with other synaptic vesicles. However, glutamatergic vesicles are defined by their ability to package glutamate for release, a property conferred by the expression of a vesicular glutamate transporter (VGLUT). VGLUTs are subject to regional, developmental, and activity-dependent changes in expression. In addition, VGLUT isoforms differ in their trafficking, which may target them to different pathways during biogenesis or after recycling, which may in turn sort them to different vesicle pools. Emerging data indicate that differences in the association of VGLUTs and other synaptic vesicle proteins with endocytic adaptors may influence their trafficking. These observations indicate that independent regulation of synaptic vesicle protein trafficking has the potential to influence synaptic vesicle protein composition, the maintenance of synaptic vesicle pools, and the release of glutamate in response to changing physiological requirements.
Topics: Animals; Central Nervous System; Endocytosis; Glutamic Acid; Humans; Membrane Proteins; Presynaptic Terminals; Protein Transport; Synaptic Transmission; Synaptic Vesicles; Vesicular Glutamate Transport Proteins
PubMed: 18472224
DOI: 10.1016/j.neuroscience.2008.03.029 -
Developmental Biology Jun 2020Arl13b is a gene known to regulate ciliogenesis. Functional alterations in this gene's activity have been associated with Joubert syndrome. We found that in Arl13 null...
Arl13b is a gene known to regulate ciliogenesis. Functional alterations in this gene's activity have been associated with Joubert syndrome. We found that in Arl13 null mouse embryos the orientation of the optic cup is inverted, such that the lens is abnormally surrounded by an inverted optic cup whose retina pigmented epithelium is oddly facing the surface ectoderm. Loss of Arl13b leads to the disruption of optic vesicle's patterning and expansion of ventral fates. We show that this phenotype is consequence of miss-regulation of Sonic hedgehog (Shh) signaling and demonstrate that the Arl13b eye phenotype can be rescued by deletion of Gli2, a downstream effector of the Shh pathway. This work identified an unexpected role of primary cilia during the morphogenetic movements required for the formation of the eye.
Topics: ADP-Ribosylation Factors; Animals; Body Patterning; Bone Morphogenetic Protein 4; Cilia; Embryonic Development; Eye; Eye Proteins; Gene Expression Regulation, Developmental; Hedgehog Proteins; Homeodomain Proteins; Humans; Lens, Crystalline; Male; Mice; Mice, Knockout; Morphogenesis; Nerve Tissue Proteins; Organogenesis; Retinal Pigment Epithelium; Signal Transduction; Wnt1 Protein; Zinc Finger Protein Gli2; Homeobox Protein SIX3
PubMed: 32169553
DOI: 10.1016/j.ydbio.2020.02.016 -
Methods in Molecular Biology (Clifton,... 2019The role of vesicle-mediated gene transfer in Acinetobacter baumannii populations has been investigated in the last decade. Importantly, outer membrane vesicles (OMVs)...
The role of vesicle-mediated gene transfer in Acinetobacter baumannii populations has been investigated in the last decade. Importantly, outer membrane vesicles (OMVs) secreted from A. baumannii cells have proven to be efficient agents of transfer of antimicrobial resistance genes to other bacterial species. However, the measurement of vesicle-mediated transfer depends on many experimental parameters. Here, we describe an experimental method useful to study transfer of DNA via membrane vesicles of A. baumannii in various bacterial populations.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Biological Transport; Gene Transfer, Horizontal; Humans; Polymerase Chain Reaction; Transport Vesicles
PubMed: 30798547
DOI: 10.1007/978-1-4939-9118-1_9 -
Synapse (New York, N.Y.) May 2015The ability of synapses to sustain neurotransmitter release during continuous activity critically relies on an efficient vesicle recycling program. Despite extensive... (Review)
Review
The ability of synapses to sustain neurotransmitter release during continuous activity critically relies on an efficient vesicle recycling program. Despite extensive research on synaptic function, the basic mechanisms of vesicle recycling remain poorly understood due to the relative inaccessibility of central synapses to conventional recording techniques. The extremely small size of synaptic vesicles, nearly five times below the diffraction-limited resolution of conventional light microscopy, has hampered efforts to define the mechanisms controlling their cycling. The complex sequence of dynamic processes that occur within the nerve terminals and link vesicle endocytosis and the subsequent round of release has been particularly difficult to study. The recent development of nanoscale-resolution imaging techniques has provided an opportunity to overcome these limitations and begin to reveal the mechanisms controlling vesicle recycling within individual nerve terminals. Here we summarize the recent advances in the implementation of super-resolution imaging and single-particle tracking approaches to study the dynamic steps of the vesicle recycling process within presynaptic terminals.
Topics: Animals; Exocytosis; Humans; Limit of Detection; Microscopy; Synaptic Vesicles
PubMed: 25522061
DOI: 10.1002/syn.21795 -
FEBS Letters May 2007During vesicular transport, the assembly of the coat complexes and the selection of cargo proteins must be coordinated with the subsequent translocation of vesicles from... (Review)
Review
During vesicular transport, the assembly of the coat complexes and the selection of cargo proteins must be coordinated with the subsequent translocation of vesicles from the donor to an acceptor compartment. Here, we review recent progress toward uncovering the molecular mechanisms that connect transport vesicles to the protein machinery responsible for cytoskeleton-mediated motility. An emerging theme is that vesicle cargo proteins, either directly or through binding interactions with coat proteins, are able to influence cytoskeletal dynamics and motor protein function. Hence, a vesicle's cargo composition may help direct its intracellular motility and targeting.
Topics: Actins; Animals; Clathrin; Cytoskeleton; Endocytosis; Golgi Apparatus; Humans; Kinesins; Microtubules; Molecular Motor Proteins; Myosins; Transport Vesicles
PubMed: 17335816
DOI: 10.1016/j.febslet.2007.01.094 -
The Journal of Physiology Dec 2007Short-term synaptic depression during repetitive activity is a common property of most synapses. Multiple mechanisms contribute to this rapid depression in... (Review)
Review
Short-term synaptic depression during repetitive activity is a common property of most synapses. Multiple mechanisms contribute to this rapid depression in neurotransmission including a decrease in vesicle fusion probability, inactivation of voltage-gated Ca(2+) channels or use-dependent inhibition of release machinery by presynaptic receptors. In addition, synaptic depression can arise from a rapid reduction in the number of vesicles available for release. This reduction can be countered by two sources. One source is replenishment from a set of reserve vesicles. The second source is the reuse of vesicles that have undergone exocytosis and endocytosis. If the synaptic vesicle reuse is fast enough then it can replenish vesicles during a brief burst of action potentials and play a substantial role in regulating the rate of synaptic depression. In the last 5 years, we have examined the impact of synaptic vesicle reuse on neurotransmission using fluorescence imaging of synaptic vesicle trafficking in combination with electrophysiological detection of short-term synaptic plasticity. These studies have revealed that synaptic vesicle reuse shapes the kinetics of short-term synaptic depression in a frequency-dependent manner. In addition, synaptic vesicle recycling helps maintain the level of neurotransmission at steady state. Moreover, our studies showed that synaptic vesicle reuse is a highly plastic process as it varies widely among synapses and can adapt to changes in chronic activity levels.
Topics: Animals; Central Nervous System; Electrophysiology; Hippocampus; Humans; Models, Neurological; Signal Transduction; Synapses; Synaptic Transmission; Synaptic Vesicles
PubMed: 17690145
DOI: 10.1113/jphysiol.2007.137745 -
Seminars in Cell & Developmental Biology Feb 2011Vesicle trafficking is a highly regulated process that transports proteins and other cargoes through eukaryotic cells while maintaining cellular organization and... (Review)
Review
Vesicle trafficking is a highly regulated process that transports proteins and other cargoes through eukaryotic cells while maintaining cellular organization and compartmental identity. In order for cargo to reach the correct destination, each step of trafficking must impart specificity. During vesicle formation, this is achieved by coat proteins, which selectively incorporate cargo into the nascent vesicle. Classically, vesicle coats are thought to dissociate shortly after budding. However, recent studies suggest that coat proteins can remain on the vesicle en route to their destination, imparting targeting specificity by physically and functionally interacting with Rab-regulated tethering systems. This review focuses on how interactions among Rab GTPases, tethering factors, SNARE proteins, and vesicle coats contribute to vesicle targeting, fusion, and coat dynamics.
Topics: Animals; Biological Transport; Coated Vesicles; Humans; Protein Binding; Protein Subunits; rab GTP-Binding Proteins
PubMed: 20643221
DOI: 10.1016/j.semcdb.2010.07.003 -
Human Pathology Nov 2017Primary seminal vesicle carcinoma is a rare entity whose diagnosis can be achieved by ruling out the main carcinomas that commonly invade the seminal vesicles. Although... (Review)
Review
Primary seminal vesicle carcinoma is a rare entity whose diagnosis can be achieved by ruling out the main carcinomas that commonly invade the seminal vesicles. Although a panel of immunohistochemical markers (cancer antigen 125, cytokeratin [CK] 7, CK20, prostate-specific antigen, and prostate-specific acid phosphatase) has been proposed as unique for primary seminal vesicle carcinoma, a reliable positive marker is lacking. In this article, we report a case of primary seminal vesicle carcinoma in a 57-year-old man. The tumor was localized to the left seminal vesicle and histologically characterized by papillae lined by broad eosinophilic cells with pleomorphic nuclei. The neoplastic cells expressed cancer antigen 125 and CK7, whereas CK20, prostate-specific antigen, and prostate-specific acid phosphatase were negative. A strong and diffuse nuclear labeling for PAX8 was detected. Because carcinomas of the colon, bladder, and prostate, the main differential diagnosis in this setting, have been reported consistently to be PAX8 negative, this marker may be very useful for a prompt diagnosis of seminal vesicle carcinoma.
Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma; Cell Nucleus; Diagnosis, Differential; Genital Neoplasms, Male; Humans; Immunohistochemistry; Magnetic Resonance Imaging; Male; Middle Aged; PAX8 Transcription Factor; Predictive Value of Tests; Seminal Vesicles
PubMed: 28506732
DOI: 10.1016/j.humpath.2017.05.003 -
Seminars in Cell & Developmental Biology Jul 2017Extracellular vesicles are nano-sized spherical bilayered proteolipids encasing various components. Cells of all domains of life actively release these vesicles to the... (Review)
Review
Extracellular vesicles are nano-sized spherical bilayered proteolipids encasing various components. Cells of all domains of life actively release these vesicles to the surroundings including various biological fluids. These extracellular vesicles are known to play pivotal roles in numerous pathophysiological functions. Extracellular vesicles have distinct characteristics, like high biocompatibility, safety, and nano-sized diameters that allow efficient drug loading capacity and long blood circulation half-life. These characteristics of extracellular vesicles have engrossed many scientists to harness them as new tools for novel delivery systems. This review will highlight the current state of the arts and problems of such extracellular vesicle-based theranostics, drug delivery and vaccines, and introduce "extracellular vesicle mimetics" as the novel alternative of extracellular vesicles. We hope to provide insights into the potential of extracellular vesicle mimetics as superior substitute to the natural extracellular vesicles that can be applied to theranostics, drug delivery, and vaccines against various diseases.
Topics: Animals; Biomimetic Materials; Drug Compounding; Drug Delivery Systems; Escherichia coli; Extracellular Vesicles; Humans; Meningitis, Bacterial; Nanostructures; Neisseria meningitidis; RNA, Small Interfering; Sepsis; Theranostic Nanomedicine; Vaccination; Vaccines
PubMed: 27916566
DOI: 10.1016/j.semcdb.2016.12.001 -
Journal of Neurogenetics Sep 2010We review mainly the work from our research group here. Our focus has been on the use of genetic methods to delineate the mechanisms of synaptic vesicle recycling and... (Review)
Review
We review mainly the work from our research group here. Our focus has been on the use of genetic methods to delineate the mechanisms of synaptic vesicle recycling and cellular trafficking. Acute temperature-sensitive paralytic mutants have been of particular value in this approach. We have primarily used screens for suppressor and enhancer mutations to identify genetic loci coding for proteins that interact with Dynamin in Drosophila. In addition, we have used reverse genetic approaches to investigate few other candidate molecules that may play a role in synaptic vesicle endocytosis. We have in particular discussed at some length the role of endocytic accessory proteins Stoned and Eps15 in vesicle recycling.
Topics: Animals; Drosophila melanogaster; Endocytosis; Molecular Biology; Presynaptic Terminals; Synaptic Transmission; Synaptic Vesicles
PubMed: 20807099
DOI: 10.3109/01677063.2010.506229