scholarly journals Research progress on vesicle cycle and neurological disorders

2021 ◽  
Vol 24 ◽  
pp. 400-412
Author(s):  
Chengcheng Zhang ◽  
Li-Juan Zhu ◽  
Ce Chen
Keyword(s):  
Synaptic Vesicles ◽  
Dynamic Balance ◽  
Synaptic Cleft ◽  
Research Progress ◽  
Triggered Release ◽  
Neuropsychiatric Diseases ◽  
Protein Receptors ◽  
Vesicle Exocytosis ◽  
Vesicle Cycle ◽  
And Function

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.

Evaluation of hippocampus in rhesus monkeys after chronic (1-year) inhalation exposure to marijuana: I. Electron microscopy

1990 ◽  
Vol 48 (3) ◽  
pp. 398-399
Author(s):  
A.M. Andrews ◽  
S.W. Wilson ◽  
A.C. Scallet ◽  
S.F. Ali ◽  
J. Bailey ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Rhesus Monkeys ◽  
Low Dose ◽  
Inhalation Exposure ◽  
Synaptic Cleft ◽  
High Dose ◽  
Withdrawal Time ◽  
Treatment Groups ◽  
Ultrastructural Evidence ◽  
Male Rhesus

Exposure of rhesus monkeys (Macaca mulatta) to marijuana via inhalation or to intravenous delta-9-tetrahydrocannabinol (THC), reportedly caused ultrastructural evidence of increased synaptic width. Chronic marijuana smoke in a single rhesus monkey examined after a six month withdrawal time caused ultrastructure changes in the septal, hippocampal and amygdala regions; the synaptic cleft was widened, electron opaque material was found in the cleft and in the pre- and postsynaptic regions, with some clumping of the synaptic vesicles. The objective of our study was to assess neuropathological alterations produced by chronic inhalation of marijuana smoke.Nineteen male rhesus monkeys, 3-5 years of age and weighing 3-8 kg, were divided into four treatment groups: a) sham control, b) placebo smoke (7 days/ week) c) low dose marijuana (2 times/week with 5 days/week sham) and d) high dose marijuana (7 times/week). A smoke exposure consisted of smoke from one cigarette (2.6% THC) burned down to 10 mm butt length. Smoke was administered via smoke generator (ADL II, Arthur D. Little, Inc. Cambridge, MA) and nose-mouth only masks (local production) equipped with one-way valves.

scholarly journals Recent Advance in the Relationship between Excitatory Amino Acid Transporters and Parkinson’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yunlong Zhang ◽  
Feng Tan ◽  
Pingyi Xu ◽  
Shaogang Qu
Keyword(s):  
Parkinson’S Disease ◽  
Amino Acid ◽  
Animal Models ◽  
Substantia Nigra ◽  
Excitatory Amino Acid ◽  
Synaptic Cleft ◽  
Dopamine Neurons ◽  
Amino Acid Transporters ◽  
Excitatory Amino Acid Transporters ◽  
And Function

Parkinson’s disease (PD) is the most common movement disorder disease in the elderly and is characterized by degeneration of dopamine neurons and formation of Lewy bodies. Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS). If glutamate is not removed promptly in the synaptic cleft, it will excessively stimulate the glutamate receptors and induce excitotoxic effects on the CNS. With lack of extracellular enzyme to decompose glutamate, glutamate uptake in the synaptic cleft is mainly achieved by the excitatory amino acid transporters (EAATs, also known as high-affinity glutamate transporters). Current studies have confirmed that decreased expression and function of EAATs appear in PD animal models. Moreover, single unilateral administration of EAATs inhibitor in the substantia nigra mimics several PD features and this is a solid evidence supporting that decreased EAATs contribute to the process of PD. Drugs or treatments promoting the expression and function of EAATs are shown to attenuate dopamine neurons death in the substantia nigra and striatum, ameliorate the behavior disorder, and improve cognitive abilities in PD animal models. EAATs are potential effective drug targets in treatment of PD and thus study of relationship between EAATs and PD has predominant medical significance currently.

scholarly journals Ca2+-dependent interaction of the growth-associated protein GAP-43 with the synaptic core complex

1997 ◽  
Vol 325 (2) ◽  
pp. 455-463 ◽  
Author(s):  
Tatsumi HARUTA ◽  
Noboru TAKAMI ◽  
Manami OHMURA ◽  
Yoshio MISUMI ◽  
Yukio IKEHARA
Keyword(s):  
Pc12 Cells ◽  
Synaptic Vesicles ◽  
Specific Protein ◽  
Cross Linking ◽  
Core Complex ◽  
Synaptic Vesicle Exocytosis ◽  
Kinase C ◽  
Vesicle Exocytosis ◽  
Chemical Cross Linking ◽  
Dependent Interaction

The synaptic vesicle exocytosis occurs by a highly regulated mechanism: syntaxin and 25 kDa synaptosome-associated protein (SNAP-25) are assembled with vesicle-associated membrane protein (VAMP) to form a synaptic core complex and then synaptotagmin participates as a Ca2+ sensor in the final step of membrane fusion. The 43 kDa growth-associated protein GAP-43 is a nerve-specific protein that is predominantly localized in the axonal growth cones and presynaptic terminal membrane. In the present study we have examined a possible interaction of GAP-43 with components involved in the exocytosis. GAP-43 was found to interact with syntaxin, SNAP-25 and VAMP in rat brain tissues and nerve growth factor-dependently differentiated PC12 cells, but not in undifferentiated PC12 cells. GAP-43 also interacted with synaptotagmin and calmodulin. These interactions of GAP-43 could be detected only when chemical cross-linking of proteins was performed before they were solubilized from the membranes with detergents, in contrast with the interaction of the synaptic core complex, which was detected without cross-linking. Experiments invitro showed that the interaction of GAP-43 with these proteins occurred Ca2+-dependently; its maximum binding with the core complex was observed at 100 μM Ca2+, whereas that of syntaxin with synaptotagmin was at 200 μM Ca2+. These values of Ca2+ concentration are close to that required for the Ca2+-dependent release of neurotransmitters. Furthermore we observed that the interaction invitro of GAP-43 with the synaptic core complex was coupled with protein kinase C-mediated phosphorylation of GAP-43. Taken together, our results suggest a novel function of GAP-43 that is involved in the Ca2+-dependent fusion of synaptic vesicles.

scholarly journals CK2 Phosphorylation is required for Regulation of Syntaxin 1A activity in Ca2+-triggered release in neuroendocrine cells

2020 ◽  
Author(s):  
Noa Barak-Broner ◽  
Dafna Singer-Lahat ◽  
Dodo Chikvashvili ◽  
Ilana Lotan
Keyword(s):  
Pc12 Cells ◽  
Structural Transition ◽  
Phosphorylation Site ◽  
Neuroendocrine Cells ◽  
Triggered Release ◽  
Juxtamembrane Region ◽  
Molecular Determinant ◽  
Vesicle Exocytosis ◽  
Summary Statement ◽  
Kinase Ck2

AbstractThe polybasic juxtamembrane region (5RK) of the plasma membrane neuronal SNARE, syntaxin1A (Syx), was shown by us to act as a fusion clamp in PC12 cells, making release dependent on stimulation by Ca2+. By using a Syx-based FRET probe, we demonstrated that 5RK is absolutely required for a depolarization-induced Ca+2-dependent, close-to-open transition (CDO) of Syx that involves the vesicular SNARE synaptobrevin2 and occurs concomitantly with Ca2+-triggered release. Here, we investigated the mechanism underlying the 5RK requirement, and identified phosphorylation of Syx at Ser-14 (S14) by protein kinase CK2 as a crucial molecular determinant. Following biochemical verification that both endogenous Syx and CSYS are constitutively S14 phosphorylated in PC12 cells, dynamic FRET analysis of phospho-null and phospho-mimetic mutants of CSYS and the use of a CK2 inhibitor revealed that it is the S14 phosphorylation that confers the 5RK requirement. Concomitant amperometric analysis of catecholamine release revealed that the phospho-null mutants do not support release, spontaneous and evoked. Collectively, these results identify a functionally important CK2 phosphorylation site in Syx that is required for 5RK-regulation of CDO and for concomitant Ca2+-triggered release.Summary statementMany phospho-proteins participate in vesicle exocytosis. We show that a recently identified structural transition of syntaxin1A that accompanies Ca2+-regulated exocytosis in neuroendocrine cells is controlled by CK2 phosphorylation of syntaxin1A.

scholarly journals The Expression and Function of Circadian Rhythm Genes in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yanan Jiang ◽  
Xiuyun Shen ◽  
Moyondafoluwa Blessing Fasae ◽  
Fengnan Zhi ◽  
Lu Chai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Pathogenic Mechanism ◽  
Research Progress ◽  
Biological Processes ◽  
And Function ◽  
Novel Therapeutic

Hepatocellular carcinoma (HCC) is among the most common and lethal form of cancer worldwide. However, its diagnosis and treatment are still dissatisfactory, due to limitations in the understanding of its pathogenic mechanism. Therefore, it is important to elucidate the molecular mechanisms and identify novel therapeutic targets for HCC. Circadian rhythm-related genes control a variety of biological processes. These genes play pivotal roles in the initiation and progression of HCC and are potential diagnostic markers and therapeutic targets. This review gives an update on the research progress of circadian rhythms, their effects on the initiation, progression, and prognosis of HCC, in a bid to provide new insights for the research and treatment of HCC.

scholarly journals The Fine Structure of Synapses in the Ciliary Ganglion of the Chick

1960 ◽  
Vol 7 (1) ◽  
pp. 31-36 ◽  
Author(s):  
A. J. de Lorenzo
Keyword(s):  
Fine Structure ◽  
Synaptic Vesicles ◽  
Ganglion Cells ◽  
Single Cells ◽  
Synaptic Cleft ◽  
Structural Features ◽  
Ciliary Ganglion ◽  
Single Axon ◽  
Electron Microscopes ◽  
Electron Microscope Image

Ciliary ganglia of chick embryos and newly hatched chicks were examined in the light and electron microscopes. Particular attention was given to the fine structure of calyciform synapses, which are characteristically found in ciliary ganglia of birds. The calyciform endings are characterized by large expansions of the presynaptic axons upon ganglion cells, and the terminal processes extend over a considerable area of the cell surface. Often, indeed they appear to envelop the cell. In the electron microscope image, the appositional membranes are separated by a space about 300 to 400 A wide; i.e., the synaptic cleft. At irregularly spaced regions, the appositional membranes show areas of increased density. The presynaptic processes contain clusters of synaptic vesicles, localized at these dense regions. Thus the fine structure complex typical of other synapses is evident. The unique structural features of this synapse are as follows: (a) The calyx or presynaptic terminal derives from a single axon, does not arborize, and terminates upon a single ganglion cell. Thus, unlike the classical bouton terminal, this represents an anatomical device for firing single cells by single axons. (b) The surface area in contiguity, i.e., the area of appositional membranes, is far more extensive than the bouton terminal. The fine structure of this synapse is compared with others, for example, the classical boutons terminaux and purely electrical synapses, in an attempt to correlate fine structure with function.

Endocannabinoid signals in the developmental programming of delayed-onset neuropsychiatric and metabolic illnesses

2013 ◽  
Vol 41 (6) ◽  
pp. 1569-1576 ◽  
Author(s):  
Erik Keimpema ◽  
Daniela Calvigioni ◽  
Tibor Harkany
Keyword(s):  
Prescription Drugs ◽  
Maternal Nutrition ◽  
System Development ◽  
Nervous System Development ◽  
Molecular Evidence ◽  
Critical Periods ◽  
Affected Offspring ◽  
Neuropsychiatric Diseases ◽  
Maternal Programming ◽  
And Function

It is increasingly recognized that maternal exposure to metabolic (nutritional) stimuli, infections, illicit or prescription drugs and environmental stressors during pregnancy can predispose affected offspring to developing devastating postnatal illnesses. If detrimental maternal stimuli coincide with critical periods of tissue production and organogenesis then they can permanently derail key cellular differentiation programs. Maternal programming can thus either provoke developmental failure directly (‘direct hit’) or introduce latent developmental errors that enable otherwise sub-threshold secondary stressors to manifest as disease (‘double hit’) postnatally. Accumulating evidence suggests that nervous system development is tightly controlled by maternal metabolic stimuli, and whose synaptic wiring and integrative capacity are adversely affected by dietary and hormonal challenges, infections or episodes of illicit drug use. Endocannabinoids, a family of signal lipids derived from polyunsaturated fatty acids, have been implicated in neuronal fate determination, the control of axonal growth, synaptogenesis and synaptic neurotransmission. Therefore the continuum and interdependence of endocannabinoid actions during the formation and function of synapses together with dynamic changes in focal and circulating endocannabinoid levels upon maternal nutritional imbalance suggest that endocannabinoids can execute the ‘reprogramming’ of specific neuronal networks. In the present paper, we review molecular evidence suggesting that maternal nutrition and metabolism during pregnancy can affect the formation and function of the hippocampus and hypothalamus by altering endocannabinoid signalling such that neuropsychiatric diseases and obesity respectively ensue in affected offspring. Moreover, we propose that the placenta, fetal adipose and nervous tissues interact via endocannabinoid signals. Thus endocannabinoids are hypothesized to act as a molecular substrate of maternal programming.

scholarly journals Genetic Analysis of Collagen Q: Roles in Acetylcholinesterase and Butyrylcholinesterase Assembly and in Synaptic Structure and Function

1999 ◽  
Vol 144 (6) ◽  
pp. 1349-1360 ◽  
Author(s):  
Guoping Feng ◽  
Eric Krejci ◽  
Jordi Molgo ◽  
Jeanette M. Cunningham ◽  
Jean Massoulié ◽  
...  
Keyword(s):  
Neuromuscular Junctions ◽  
Synaptic Cleft ◽  
Neuromuscular Function ◽  
Nerve Terminals ◽  
Compensatory Mechanisms ◽  
Structural Mechanism ◽  
Synaptic Structure ◽  
Cardiac Muscles ◽  
And Function ◽  
Early Phases

Acetylcholinesterase (AChE) occurs in both asymmetric forms, covalently associated with a collagenous subunit called Q (ColQ), and globular forms that may be either soluble or membrane associated. At the skeletal neuromuscular junction, asymmetric AChE is anchored to the basal lamina of the synaptic cleft, where it hydrolyzes acetylcholine to terminate synaptic transmission. AChE has also been hypothesized to play developmental roles in the nervous system, and ColQ is also expressed in some AChE-poor tissues. To seek roles of ColQ and AChE at synapses and elsewhere, we generated ColQ-deficient mutant mice. ColQ−/− mice completely lacked asymmetric AChE in skeletal and cardiac muscles and brain; they also lacked asymmetric forms of the AChE homologue, butyrylcholinesterase. Thus, products of the ColQ gene are required for assembly of all detectable asymmetric AChE and butyrylcholinesterase. Surprisingly, globular AChE tetramers were also absent from neonatal ColQ−/− muscles, suggesting a role for the ColQ gene in assembly or stabilization of AChE forms that do not themselves contain a collagenous subunit. Histochemical, immunohistochemical, toxicological, and electrophysiological assays all indicated absence of AChE at ColQ−/− neuromuscular junctions. Nonetheless, neuromuscular function was initially robust, demonstrating that AChE and ColQ do not play obligatory roles in early phases of synaptogenesis. Moreover, because acute inhibition of synaptic AChE is fatal to normal animals, there must be compensatory mechanisms in the mutant that allow the synapse to function in the chronic absence of AChE. One structural mechanism appears to be a partial ensheathment of nerve terminals by Schwann cells. Compensation was incomplete, however, as animals lacking ColQ and synaptic AChE failed to thrive and most died before they reached maturity.

scholarly journals The synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration

2012 ◽  
Vol 196 (2) ◽  
pp. 261-276 ◽  
Author(s):  
Adam Haberman ◽  
W. Ryan Williamson ◽  
Daniel Epstein ◽  
Dong Wang ◽  
Srisha Rina ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Transmembrane Protein ◽  
Primary Defect ◽  
Endosomal Sorting ◽  
Synaptic Vesicle Exocytosis ◽  
Cathepsin Proteases ◽  
Core Proteins ◽  
Protein Receptors ◽  
Vesicle Exocytosis ◽  
Photoreceptor Neurons

Soluble NSF attachment protein receptors (SNAREs) are the core proteins in membrane fusion. The neuron-specific synaptic v-SNARE n-syb (neuronal Synaptobrevin) plays a key role during synaptic vesicle exocytosis. In this paper, we report that loss of n-syb caused slow neurodegeneration independent of its role in neurotransmitter release in adult Drosophila melanogaster photoreceptor neurons. In addition to synaptic vesicles, n-Syb localized to endosomal vesicles. Loss of n-syb lead to endosomal accumulations, transmembrane protein degradation defects, and a secondary increase in autophagy. Our evidence suggests a primary defect of impaired delivery of vesicles that contain degradation proteins, including the acidification-activated Cathepsin proteases and the neuron-specific proton pump and V0 adenosine triphosphatase component V100. Overexpressing V100 partially rescued n-syb–dependent degeneration through an acidification-independent endosomal sorting mechanism. Collectively, these findings reveal a role for n-Syb in a neuron-specific sort-and-degrade mechanism that protects neurons from degeneration. Our findings further shed light on which intraneuronal compartments exhibit increased or decreased neurotoxicity.

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