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Synaptic vesicle

Antonella Sferra, Fabiana Fattori, Teresa Rizza, Elsabetta Flex, Emanuele Bellacchio, Alessandro Bruselles, Stefania Petrini, Serena Cecchetti, Massimo Teson, Fabrizia Restaldi, Andrea Ciolfi, Filippo M Santorelli, Ginevra Zanni, Sabina Barresi, Claudia Castiglioni, Marco Tartaglia, Enrico Bertini
Microtubules participate in fundamental cellular processes, including chromosomal segregation and cell division, migration, and intracellular trafficking. Their proper function is required for correct central nervous system development and operative preservation, and mutations in genes coding tubulins, the constituting units of microtubules, underlie a family of neurodevelopmental and neurodegenerative diseases, collectively known as "tubulinopathies", characterized by a wide range of neuronal defects resulting from defective proliferation, migration, and function...
March 14, 2018: Human Molecular Genetics
Joseph E Pick, Edward B Ziff
A fundamental property of the brain is its ability to modify its function in response to its own activity. This ability for self-modification depends to a large extent on synaptic plasticity. It is now appreciated that for excitatory synapses, a significant part of synaptic plasticity depends upon changes in the post synaptic response to glutamate released from nerve terminals. Modification of the post synaptic response depends, in turn, on changes in the abundances of AMPA receptors in the post synaptic membrane...
March 12, 2018: Molecular and Cellular Neurosciences
Geoffrey Masuyer, Sicai Zhang, Sulyman Barkho, Yi Shen, Linda Henriksson, Sara Košenina, Min Dong, Pål Stenmark
Botulinum neurotoxins (BoNTs) are among the most potent toxins known and are also used to treat an increasing number of medical disorders. There are seven well-established serotypes (BoNT/A-G), which all act as zinc-dependent endopeptidases targeting specific members of the SNARE proteins required for synaptic vesicle exocytosis in neurons. A new toxin serotype, BoNT/X, was recently identified. It cleaves not only the canonical targets, vesicle associated membrane proteins (VAMP) 1/2/3 at a unique site, but also has the unique ability to cleave VAMP4/5 and Ykt6...
March 14, 2018: Scientific Reports
Mary E Orczykowski, Kevin R Arndt, Lauren E Palitz, Brian C Kramer, Monica A Pessina, Adrian L Oblak, Seth P Finklestein, Farzad Mortazavi, Douglas L Rosene, Tara L Moore
Stroke results in enduring damage to the brain which is accompanied by innate neurorestorative processes, such as reorganization of surviving circuits. Nevertheless, patients are often left with permanent residual impairments. Cell based therapy is an emerging therapeutic that may function to enhance the innate neurorestorative capacity of the brain. We previously evaluated human umbilical tissue-derived cells (hUTC) in our non-human primate model of cortical injury limited to the hand area of primary motor cortex...
March 11, 2018: Experimental Neurology
Yi Yu, Su Chen, Xiaoqiang Mo, Jihong Gong, Chenhong Li, Xiaofei Yang
Complexins, binding to assembling soluble NSF-attachment protein receptor (SNARE) complexes, activate Ca2+ triggered exocytosis and clamp spontaneous release in the presynaptic terminal. Functions of complexin are structural dependent and mechanistically distinct. To further understand the functional/structural dependence of complexin, here we show that the accessory and central α-helices of complexin are sufficient in activation of Ca2+ triggered vesicle fusion but not in clamping spontaneous release. Targeting the two α-helices to synaptic vesicle suppresses spontaneous release, thus further emphasizing the importance of curvature membrane localization in clamping function...
2018: Frontiers in Molecular Neuroscience
Priscila A C Valadão, Matheus P S M Gomes, Bárbara C Aragão, Hermann A Rodrigues, Jéssica N Andrade, Rubens Garcias, Julliane V Joviano-Santos, Murilo A Luiz, Wallace L Camargo, Lígia A Naves, Christopher Kushmerick, Walter L G Cavalcante, Márcia Gallacci, Itamar C G de Jesus, Silvia Guatimosim, Cristina Guatimosim
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by chorea, incoordination, and psychiatric and behavioral symptoms. The leading cause of death in HD patients is aspiration pneumonia, associated with respiratory dysfunction, decreased respiratory muscle strength and dysphagia. Although most of the motor symptoms are derived from alterations in the central nervous system, some might be associated with changes in the components of motor units (MU). To explore this hypothesis, we evaluated morphofunctional aspects of the diaphragm muscle in a mouse model of HD (BACHD)...
March 9, 2018: Neurochemistry International
Shruti Thapliyal, Amruta Vasudevan, Yongming Dong, Jihong Bai, Sandhya P Koushika, Kavita Babu
The C. elegans ortholog of mammalian calsyntenins, CASY-1, is an evolutionarily conserved type-I transmembrane protein that is highly enriched in the nervous system. Mammalian calsyntenins are strongly expressed at inhibitory synapses, but their role in synapse development and function is still elusive. Here, we report a crucial role for CASY-1 in regulating GABAergic synaptic transmission at the C. elegans neuromuscular junction (NMJ). The shorter isoforms of CASY-1; CASY-1B and CASY-1C, express and function in GABA motor neurons where they regulate GABA neurotransmission...
March 12, 2018: PLoS Genetics
Takeshi Sakaba
Synaptic contacts mediate information transfer between neurons. The calyx of Held, a large synapse in the mammalian auditory brainstem, has been used as a model system for the mechanism of transmitter release from the presynaptic terminal for the last 20 years. By applying simultaneous recordings from pre- and postsynaptic compartments, the calcium-dependence of the kinetics of transmitter release has been quantified. A single pool of readily releasable vesicles cannot explain the time course of release during repetitive activity...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
Lifu Sheng, Iryna Leshchyns'ka, Vladimir Sytnyk
The neural cell adhesion molecule 2 (NCAM2) is encoded by a gene on chromosome 21 in humans. NCAM2 accumulates in synapses, but its role in regulation of synapse formation remains poorly understood. We demonstrate that an increase in NCAM2 levels results in increased instability of dendritic protrusions and reduced conversion of protrusions to dendritic spines in mouse cortical neurons. NCAM2 overexpression induces an increase in the frequency of submembrane Ca2+ spikes localized in individual dendritic protrusions and promotes propagation of submembrane Ca2+ spikes over segments of dendrites or the whole dendritic tree...
March 7, 2018: Cerebral Cortex
Silvia Uccella, Stefano La Rosa, Marco Volante, Mauro Papotti
Neuroendocrine neoplasms (NENs) are a heterogeneous group of epithelial neoplastic proliferations that irrespective of their primary site share features of neural and endocrine differentiation including the presence of secretory granules, synaptic-like vesicles, and the ability to produce amine and/or peptide hormones. NENs encompass a wide spectrum of neoplasms ranging from well-differentiated indolent tumors to highly aggressive poorly differentiated neuroendocrine carcinomas. Most cases arise in the digestive system and in thoracic organs, i...
March 9, 2018: Endocrine Pathology
Jessika C Bridi, Frank Hirth
Parkinson's disease (PD) is characterized by intracellular inclusions of aggregated and misfolded α-Synuclein (α-Syn), and the loss of dopaminergic (DA) neurons in the brain. The resulting motor abnormalities mark the progression of PD, while non-motor symptoms can already be identified during early, prodromal stages of disease. Recent studies provide evidence that during this early prodromal phase, synaptic and axonal abnormalities occur before the degenerative loss of neuronal cell bodies. These early phenotypes can be attributed to synaptic accumulation of toxic α-Syn...
2018: Frontiers in Neuroscience
Federica Bosco, Pierluigi Valente, Marco Milanese, Alessandra Piccini, Mirko Messa, Giambattista Bonanno, Paul Lombroso, Pietro Baldelli, Fabio Benfenati, Silvia Giovedì
The striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific phosphatase involved in synaptic transmission. The current hypothesis on STEP function holds that it opposes synaptic strengthening by dephosphorylating and inactivating key neuronal proteins involved in synaptic plasticity and intracellular signaling, such as the MAP kinases ERK1/2 and p38, as well as the tyrosine kinase Fyn. Although STEP has a predominant role at the post-synaptic level, it is also expressed in nerve terminals...
March 5, 2018: Molecular Neurobiology
Amrita Datta Chaudhuri, Raha M Dastgheyb, Seung-Wan Yoo, Amanda Trout, C Conover Talbot, Haiping Hao, Kenneth W Witwer, Norman J Haughey
Astrocytes are known to be critical regulators of neuronal function. However, relatively few mediators of astrocyte to neuron communication have been identified. Recent advancements in the biology of extracellular vesicles have begun to implicate astrocyte derived extracellular vesicles (ADEV) as mediators of astrocyte to neuron communication, suggesting that alterations in the release and/or composition of ADEVs could influence gliotransmission. TNFα and IL-1β are key mediators of glial activation and neuronal damage, but the effects of these cytokines on the release or molecular composition of ADEVs is unknown...
March 5, 2018: Cell Death & Disease
Meiyuan Yang, Yaobin Li, Lei Hu, Dan Luo, Yi Zhang, Xue Xiao, Guilin Li, Lixia Zhang, Gaochun Zhu
Lead (Pb) exposure has been shown to affect presynaptic neurotransmitter release in the animal and cell models. The mechanism by which Pb exposure impairs neurotransmitter release remains unknown. In this study, we aimed to investigate the effect of Pb exposure on synaptic vesicle protein 2C (SV2C) and its molecular mechanism. SV2C promoter region contains a neuron-restrictive silencer element (NRSE) binding motif. Neuron-restrictive silencer factor (NRSF) is a transcription repressor that regulates gene expression by binding to NRSE...
March 2, 2018: Toxicology
Zhiping Jiang, Jessica D Flynn, Walter E Teague, Klaus Gawrisch, Jennifer C Lee
α-Synuclein (α-Syn) is a presynaptic protein that is accumulated in its amyloid form in the brains of Parkinson's patients. Although its biological function remains unclear, α-syn has been suggested to bind to synaptic vesicles and facilitate neurotransmitter release. Recently, studies have found that α-syn induces membrane tubulation, highlighting a potential mechanism for α-syn to stabilize highly curved membrane structures which could have both functional and dysfunctional consequences. To understand how membrane remodeling by α-syn affects amyloid formation, we have studied the α-syn aggregation process in the presence of phosphatidylglycerol (PG) micellar tubules, which were the first reported example of membrane tubulation by α-syn...
March 1, 2018: Biochimica et Biophysica Acta
Md Mohibbullah, Jae-Suk Choi, Mohammad Maqueshudul Haque Bhuiyan, Md Nazmul Haque, Md Khalilur Rahman, Il Soo Moon, Yong-Ki Hong
Exogenous neurotrophins can induce neuronal differentiation, outgrowth, survival, and synaptic function in the central nervous system. In primary cultures of rat hippocampal neurons, an ethanol extract of the red alga Gracilariopsis chorda (GCE) and its active compound arachidonic acid (AA) significantly increased the densities of dendritic filopodia and spines, promoted the expression of presynaptic vesicle protein 2 (SV2) and postsynaptic density protein 95 (PSD-95), induced robust synaptogenesis, and increased the expression of cell division control protein 42 (CDC42) and actin-related protein 2 (ARP2), which are important for actin organization in dendritic protrusions, and facilitated presynaptic plasticity by increasing the size of the synaptic vesicle pool at presynaptic nerve terminals...
March 2, 2018: Journal of Medicinal Food
Saak V Ovsepian, Valerie B O'Leary, Laszlo Zaborszky, Vasilis Ntziachristos, Oliver J Dolly
The synaptic vesicle cycle (SVC) holds center stage in the biology of presynaptic terminals. Through recurrent exocytosis and endocytosis, it facilitates a sequence of events enabling chemical neurotransmission between functionally related neurons. As a fundamental process that links the interior of nerve cells with their environment, the SVC is also critical for signaling and provides an entry route for a range of pathogens and toxins, enabling detrimental effects. In Alzheimer's disease, the SVC is both the prime site of amyloid β production and toxicity...
February 26, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Hiroyuki Fukuda, Eri Imagawa, Kohei Hamanaka, Atsushi Fujita, Satomi Mitsuhashi, Satoko Miyatake, Takeshi Mizuguchi, Atsushi Takata, Noriko Miyake, Uri Kramer, Naomichi Matsumoto, Aviva Fattal-Valevski
SNAP25 is a core component of the soluble N-ethylmaleimide-sensitive factor attachment receptor complex, which plays a critical role in synaptic vesicle exocytosis. To date, six de novo SNAP25 mutations have been reported in patients with neurological features including seizures, intellectual disability, severe speech delay, and cerebellar ataxia. Here, we analyzed an Israeli family with two affected siblings showing seizures and cerebellar dysfunction by whole-exome sequencing, and identified a novel missense SNAP25 mutation (c...
February 28, 2018: Journal of Human Genetics
Richard G Held, Pascal S Kaeser
Synaptic vesicle exocytosis relies on the tethering of release ready vesicles close to voltage-gated Ca2+ channels and specific lipids at the future site of fusion. This enables rapid and efficient neurotransmitter secretion during presynaptic depolarization by an action potential. Extensive research has revealed that this tethering is mediated by an active zone, a protein dense structure that is attached to the presynaptic plasma membrane and opposed to postsynaptic receptors. Although roles of individual active zone proteins in exocytosis are in part understood, the molecular mechanisms that hold the protein scaffold at the active zone together and link it to the presynaptic plasma membrane have remained unknown...
February 2018: Open Biology
Haowen Liu, Lei Li, Wei Wang, Jihong Gong, Xiaofei Yang, Zhitao Hu
The locomotion of C. elegans is balanced by excitatory and inhibitory neurotransmitter release at neuromuscular junctions. However, the molecular mechanisms that maintain the balance of synaptic transmission remain enigmatic. Here, we investigated the function of voltage-gated Ca2+ channels in triggering spontaneous release at cholinergic and GABAergic synapses. Recordings of the miniature excitatory/inhibitory postsynaptic currents (mEPSCs and mIPSCs, respectively) showed that UNC-2/CaV2 and EGL-19/CaV1 channels are the two major triggers for spontaneous release...
February 27, 2018: Cell Reports
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