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 Acetylcholinesterase from the motor nerve terminal accumulates on the synaptic basal lamina of the myofiber.

1991 ◽  
Vol 115 (3) ◽  
pp. 755-764 ◽  
Author(s):  
L Anglister
Keyword(s):  
Basal Lamina ◽  
Ache Activity ◽  
Neuromuscular Junctions ◽  
Motor Nerve ◽  
Synaptic Cleft ◽  
Motor Nerve Terminal ◽  
Nerve Terminals ◽  
Axon Terminals ◽  
Muscle Nerve ◽  
Almost All

Acetylcholinesterase (AChE) in skeletal muscle is concentrated at neuromuscular junctions, where it is found in the synaptic cleft between muscle and nerve, associated with the synaptic portion of the myofiber basal lamina. This raises the question of whether the synaptic enzyme is produced by muscle, nerve, or both. Studies on denervated and regenerating muscles have shown that myofibers can produce synaptic AChE, and that the motor nerve may play an indirect role, inducing myofibers to produce synaptic AChE. The aim of this study was to determine whether some of the AChE which is known to be made and transported by the motor nerve contributes directly to AChE in the synaptic cleft. Frog muscles were surgically damaged in a way that caused degeneration and permanent removal of all myofibers from their basal lamina sheaths. Concomitantly, AChE activity was irreversibly blocked. Motor axons remained intact, and their terminals persisted at almost all the synaptic sites on the basal lamina in the absence of myofibers. 1 mo after the operation, the innervated sheaths were stained for AChE activity. Despite the absence of myofibers, new AChE appeared in an arborized pattern, characteristic of neuromuscular junctions, and its reaction product was concentrated adjacent to the nerve terminals, obscuring synaptic basal lamina. AChE activity did not appear in the absence of nerve terminals. We concluded therefore, that the newly formed AChE at the synaptic sites had been produced by the persisting axon terminals, indicating that the motor nerve is capable of producing some of the synaptic AChE at neuromuscular junctions. The newly formed AChE remained adherent to basal lamina sheaths after degeneration of the terminals, and was solubilized by collagenase, indicating that the AChE provided by nerve had become incorporated into the basal lamina as at normal neuromuscular junctions.

scholarly journals Antidepressant Interactions with the NMDA NR1-1b Subunit

2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Richard Raabe ◽  
Lisa Gentile
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Tricyclic Antidepressants ◽  
Synaptic Cleft ◽  
Ionotropic Glutamate Receptors ◽  
Ionotropic Glutamate Receptor ◽  
Nerve Terminals ◽  
Presynaptic Neuron ◽  
Presynaptic Nerve Terminals ◽  
And Function ◽  
Norepinephrine Reuptake

The targets for tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and selective norepinephrine reuptake inhibitors (SNRIs) are known to be the serotonin and norepinephrine transport (reuptake) proteins which are embedded in presynaptic nerve terminals and function to bring these neurotransmitters from the synaptic cleft back into the presynaptic neuron. Using a combination of intrinsic and extrinsic fluorescence quenching, Stern-Volmer analysis, and protease protection assays, we have shown that therapeutics from each of these three classes of antidepressants bind to the extracellular S1S2 domain of the NR1-1b subunit of the NMDA receptor. These results are in agreement with recent work from our lab demonstrating the interaction of antidepressants with the S1S2 domain of the GluR2 subunit of the AMPA receptor, another member of the ionotropic glutamate receptor subfamily, as well as work from other labs, and continue the discussion of the involvement of ionotropic glutamate receptors in depression.

scholarly journals Glial response to hypoxia in trachealess mutants induces synapse remodeling

2019 ◽  
Author(s):  
Pei-Yi Chen ◽  
Yi-Wei Tsai ◽  
Angela Giangrande ◽  
Cheng-Ting Chien
Keyword(s):  
Synaptic Transmission ◽  
Neuromuscular Junctions ◽  
Hypoxia Inducible Factor ◽  
Wild Type ◽  
Animal Cells ◽  
Hypoxia Response ◽  
Synaptic Remodeling ◽  
Environmental Perturbations ◽  
Synaptic Structure ◽  
And Function

AbstractSynaptic structure and activity are sensitive to environmental alterations. Modulation of synaptic morphology and function is often induced by signals from glia. However, the process by which glia mediate synaptic responses to environmental perturbations such as hypoxia remains unknown. Here, we report that, in the Drosophila trachealess (trh) mutant, smaller synaptic boutons form clusters named bunch boutons appear at larval neuromuscular junctions (NMJs), which is induced by the reduction of internal oxygen levels due to defective tracheal branches. Thus, the bunch bouton phenotype in the trh mutant is suppressed by hyperoxia, and recapitulated in wild-type larvae raised under hypoxia. We further show that hypoxia-inducible factor (HIF)-1α/Similar (Sima) is critical in mediating hypoxia-induced bunch bouton formation. Sima upregulates the level of the Wnt/Wingless (Wg) signal in glia, leading to reorganized microtubule structures within presynaptic sites. Finally, hypoxia-induced bunch boutons maintain normal synaptic transmission at the NMJs, which is crucial for coordinated larval locomotion.Author summaryOxygen is essential for animals to maintain their life such as growth, metabolism, responsiveness, and movement. It is therefore important to understand how animal cells trigger hypoxia response and adapt to hypoxia thereafter. Both mammalian vascular and insect tracheal branches are induced to enhance the oxygen delivery. However, the study of hypoxia response in the nervous system remains limited. In this study, we assess the morphology of Drosophila neuromuscular junctions (NMJs), a model system to study development and function of synapses, in two hypoxia conditions, one with raising wild-type larvae in hypoxia, and the other in the trachealess (trh) mutant in which the trachea is defective, causing insufficient oxygen supply. Interestingly, glia, normally wrapping the axons of NMJs, invade into synapse and trigger Wg signals to reconstitute the synaptic structure under hypoxia. This synaptic remodeling maintains the synaptic transmission of synapse, which associate the locomotor behavior of larvae.

scholarly journals Drosophila MIC60/mitofilin conducts dual roles in mitochondrial motility and crista structure

2017 ◽  
Vol 28 (24) ◽  
pp. 3471-3479 ◽  
Author(s):  
Pei-I Tsai ◽  
Amanda M. Papakyrikos ◽  
Chung-Han Hsieh ◽  
Xinnan Wang
Keyword(s):  
Neuromuscular Junctions ◽  
Cellular Level ◽  
Dual Roles ◽  
Protein Levels ◽  
Mitochondrial Homeostasis ◽  
Synaptic Structure ◽  
Microtubule Motors ◽  
Mitochondrial Motility ◽  
And Function

MIC60/mitofilin constitutes a hetero-oligomeric complex on the inner mitochondrial membranes to maintain crista structure. However, little is known about its physiological functions. Here, by characterizing Drosophila MIC60 mutants, we define its roles in vivo. We discover that MIC60 performs dual functions to maintain mitochondrial homeostasis. In addition to its canonical role in crista membrane structure, MIC60 regulates mitochondrial motility, likely by influencing protein levels of the outer mitochondrial membrane protein Miro that anchors mitochondria to the microtubule motors. Loss of MIC60 causes loss of Miro and mitochondrial arrest. At a cellular level, loss of MIC60 disrupts synaptic structure and function at the neuromuscular junctions. The dual roles of MIC60 in both mitochondrial crista structure and motility position it as a crucial player for cellular integrity and survival.

Dynamics of nerve-muscle interaction in developing and mature neuromuscular junctions

1995 ◽  
Vol 75 (4) ◽  
pp. 789-834 ◽  
Author(s):  
A. D. Grinnell
Keyword(s):  
Synapse Formation ◽  
Neuromuscular Junctions ◽  
Structure And Function ◽  
Axon Pathfinding ◽  
Control Of Gene Expression ◽  
Synaptic Structure ◽  
Dynamic Cell ◽  
Nerve Muscle ◽  
And Function ◽  
Motoneuron Cell

Neuromuscular connections have long served as models of synaptic structure and function. They also provide illuminating insights into the dynamic cell-cell interactions governing synaptogenesis, neuromuscular differentiation, and the maintenance of effective function. This paper reviews recent advances in our understanding of the regulatory and inductive interactions involved in motor axon pathfinding, target recognition, bidirectional control of gene expression during synapse formation, motoneuron cell death, terminal rearrangement, and the ongoing remodeling of synaptic number, structure, and function to adjust to growth and changes in use.

scholarly journals A presynaptic spectrin network controls active zone assembly and neurotransmitter release

2019 ◽  
Author(s):  
Qi Wang ◽  
Lindsey Friend ◽  
Rosario Vicidomini ◽  
Tae Hee Han ◽  
Peter Nguyen ◽  
...  
Keyword(s):  
Active Zone ◽  
Neurotransmitter Release ◽  
Synaptic Cleft ◽  
Structure And Function ◽  
Dynamic Changes ◽  
Synaptic Structure ◽  
Synaptic Boutons ◽  
Active Zones ◽  
And Function ◽  
Spectrin Network

ABSTRACTWe have previously reported that Drosophila Tenectin (Tnc) recruits αPS2/βPS integrin to ensure structural and functional integrity at larval NMJs (Wang et al., 2018). In muscles, Tnc/integrin engages the spectrin network to regulate the size and architecture of synaptic boutons. In neurons, Tnc/integrin controls neurotransmitter release. Here we show that presynaptic Tnc/integrin modulates the synaptic accumulation of key active zone components, including the Ca2+ channel Cac and the active zone scaffold Brp. Presynaptic α-Spectrin appears to be both required and sufficient for the recruitment of Cac and Brp. We visualized the endogenous α-Spectrin and found that Tnc controls spectrin recruitment at synaptic terminals. Thus, Tnc/integrin anchors the presynaptic spectrin network and ensures the proper assembly and function of the active zones. Since pre- and postsynaptic Tnc/integrin limit each other, we hypothesize that this pathway links dynamic changes within the synaptic cleft to changes in synaptic structure and function.

The Effect of Lidocaine on Twitch Potentiation and Repetitive Neural ActivityProduced by Soman and Neostigmine

1971 ◽  
Vol 49 (5) ◽  
pp. 464-468 ◽  
Author(s):  
H. Lowndes ◽  
D. D. Johnson
Keyword(s):  
Electrical Activity ◽  
Phrenic Nerve ◽  
Neuromuscular Junctions ◽  
Neuromuscular Function ◽  
Repetitive Firing ◽  
Nerve Terminals ◽  
Drug Induced ◽  
Twitch Potentiation ◽  
Presynaptic Nerve Terminals ◽  
Isolated Rat

Soman and neostigmine produce twitch potentiation in the isolated rat phrenic nerve – diaphragm preparation by initiating repetitive electrical activity at neuromuscular junctions. This is associated with repetitive impulses in the phrenic nerve. Lidocaine abolishes the repetitive firing in both the phrenic nerve and diaphragm. This effect is produced by concentrations of lidocaine that have no effect on normal neuromuscular function as indicated by the absence of an effect on normal twitch or tetanic responses. These results indicate that the mechanism by which lidocaine abolishes drug-induced twitch potentiation involves the presynaptic nerve terminals.

Structural and functional maturation of presynaptic nerve endings under the control of transsynaptic signalling

e-Neuroforum ◽  
2012 ◽  
Vol 18 (2) ◽  
Author(s):  
Nina Wittenmayer ◽  
Thomas Dresbach
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Synaptic Cleft ◽  
Nerve Cells ◽  
Synaptic Structure ◽  
Molecular Events ◽  
And Function ◽  
Postsynaptic Differentiation ◽  
Adhesive Contacts

AbstractSynapse assembly is the cellular mechanism that mediates the generation of physical con­nections between nerve cells and, thus, al­lows for the establishment of functional con­nectivity in the brain. The biogenesis of a syn­apse requires a set of highly coordinated mo­lecular events, ranging from initial forma­tion of adhesive contacts between an axon and a dendrite, followed by the recruitment and precise arrangement of synaptic organ­elles and proteins on both sides of the syn­aptic cleft, and culminating in the mainte­nance and remodelling of the exquisite archi­tecture of a differentiated, i.e. mature, synap­tic junction. Both the postsynaptic and the presynaptic compartment are thought to un­dergo stages of maturation that change and shape synaptic structure and function in a characteristic way. Recent evidence suggests that transsynaptic signalling, elicited by post­synaptic cell adhesion molecules, regulates the molecular events underlying presynap­tic maturation. Thus, synaptic cell adhesion molecules, apart from physically connecting nerve cells, emerge as coordinators of presyn­aptic and postsynaptic differentiation across the synaptic cleft.

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.

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