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 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.

Reversible Effects of Hyperosmolar Sucrose on Frog Sympathetic Ganglion

1973 ◽  
Vol 31 ◽  
pp. 534-535
Author(s):  
E. Minker ◽  
W. K. Riker ◽  
N. J. Russell
Keyword(s):  
Synaptic Transmission ◽  
Sympathetic Ganglion ◽  
Neuromuscular Junctions ◽  
Extracellular Recording ◽  
Sympathetic Ganglia ◽  
Discharge Frequency ◽  
Ringer’S Solution ◽  
Synaptic Structure ◽  
Structural Recovery ◽  
Saline Solutions

Saline solutions made hyperosmotic by addition of sucrose increase the discharge frequency of miniature spontaneous junctional potentials at neuromuscular junctions and sympathetic ganglia and can alter structure in both muscle and nerve. Since effects of such solutions on synaptic structure are unknown, we have investigated the influence of hyperosmolarity on function and ultrastructure in synaptic regions of isolated abdominal sympathetic ganglia of the bullfrog, Rana catesbiana.Synaptic transmission was monitored by extracellular recording of postganglionic responses to supramaximal.preganglionic stimulation (0.3 Hz). Ganglia were first equilibrated in normal frog Ringer's solution, then transferred to test solutions, and some ganglia were subsequently returned to normal Ringer's to examine functional and structural recovery.

scholarly journals Activation of Hypoxia Response in Endothelial Cells Contributes to Ischemic Cardioprotection

2013 ◽  
Vol 33 (16) ◽  
pp. 3321-3329 ◽  
Author(s):  
Risto Kerkelä ◽  
Sara Karsikas ◽  
Zoltan Szabo ◽  
Raisa Serpi ◽  
Johanna Magga ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Small Molecule ◽  
Target Genes ◽  
Systolic Function ◽  
Hypoxia Inducible Factor ◽  
Wild Type ◽  
Hypoxia Response ◽  
Lv Systolic Function ◽  
Collateral Vessels ◽  
Endothelial Nitric Oxide

Small-molecule inhibition of hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs) is being explored for the treatment of anemia. Previous studies have suggested that HIF-P4H-2 inhibition may also protect the heart from an ischemic insult.Hif-p4h-2gt/gtmice, which have 76 to 93% knockdown ofHif-p4h-2mRNA in endothelial cells, fibroblasts, and cardiomyocytes and normoxic stabilization of Hif-α, were subjected to ligation of the left anterior descending coronary artery (LAD). Hif-p4h-2 deficiency resulted in increased survival, better-preserved left ventricle (LV) systolic function, and a smaller infarct size. Surprisingly, a significantly larger area of the LV remained perfused during LAD ligation inHif-p4h-2gt/gthearts than in wild-type hearts. However, no difference was observed in collateral vessels, while the size of capillaries, but not their number, was significantly greater inHif-p4h-2gt/gthearts than in wild-type hearts.Hif-p4h-2gt/gtmice showed increased cardiac expression of endothelial Hif target genes for Tie-2, apelin, APJ, and endothelial nitric oxide (NO) synthase (eNOS) and increased serum NO concentrations. Remarkably, blockage of Tie-2 signaling was sufficient to normalize cardiac apelin and APJ expression and resulted in reversal of the enlarged-capillary phenotype and ischemic cardioprotection inHif-p4h-2gt/gthearts. Activation of the hypoxia response by HIF-P4H-2 inhibition in endothelial cells appears to be a major determinant of ischemic cardioprotection and justifies the exploration of systemic small-molecule HIF-P4H-2 inhibitors for ischemic heart disease.

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.

scholarly journals Localization and function of Xinα in mouse skeletal muscle

2013 ◽  
Vol 304 (10) ◽  
pp. C1002-C1012 ◽  
Author(s):  
Han-Zhong Feng ◽  
Qinchuan Wang ◽  
Rebecca S. Reiter ◽  
Jenny L.-C. Lin ◽  
Jim J.-C. Lin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Heart Development ◽  
Neuromuscular Junctions ◽  
Troponin T ◽  
Diaphragm Muscle ◽  
Myotendinous Junction ◽  
Wild Type ◽  
Adult Skeletal Muscle ◽  
Edl Muscle ◽  
And Function

The Xin repeat-containing proteins were originally found in the intercalated discs of cardiac muscle with implicated roles in cardiac development and function. A pair of paralogous genes, Xinα ( Xirp1) and Xinβ ( Xirp2), is present in mammals. Ablation of the mouse Xinα ( mXinα) did not affect heart development but caused late-onset adulthood cardiac hypertrophy and cardiomyopathy with conductive defects. Both mXinα and mXinβ are also found in the myotendinous junction (MTJ) of skeletal muscle. Here we investigated the structural and functional significance of mXinα in skeletal muscle. In addition to MTJ and the contact sites between muscle and perimysium, mXinα but not mXinβ was found in the blood vessel walls, whereas both proteins were absent in neuromuscular junctions and nerve fascicles. Coimmunoprecipitation suggested association of mXinα with talin, vinculin, and filamin, but not β-catenin, in adult skeletal muscle, consistent with our previous report of colocalization of mXinα with vinculin. Loss of mXinα in mXinα-null mice had subtle effects on the MTJ structure and the levels of several MTJ components. Diaphragm muscle of mXinα-null mice showed hypertrophy. Compared with wild-type controls, mouse extensor digitorum longus (EDL) muscle lacking mXinα exhibited no overt change in contractile and relaxation velocities or maximum force development but better tolerance to fatigue. Loaded fatigue contractions generated stretch injury in wild-type EDL muscle as indicated by a fragmentation of troponin T. This effect was blunted in mXinα-null EDL muscle. The results suggest that mXinα play a role in MTJ conductance of contractile and stretching forces.

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 The NALCN Channel Regulator UNC-80 Functions in a Subset of Interneurons To Regulate Caenorhabditis elegans Reversal Behavior

2019 ◽  
Vol 10 (1) ◽  
pp. 199-210 ◽  
Author(s):  
Chuanman Zhou ◽  
Jintao Luo ◽  
Xiaohui He ◽  
Qian Zhou ◽  
Yunxia He ◽  
...  
Keyword(s):  
Plant Hormone ◽  
Neuronal Excitability ◽  
Resting Membrane Potential ◽  
Loss Of Function ◽  
Wild Type ◽  
C Elegans ◽  
Link Type ◽  
Complex Functions ◽  
And Function ◽  
Multiple Loss

NALCN (Na+leak channel, non-selective) is a conserved, voltage-insensitive cation channel that regulates resting membrane potential and neuronal excitability. UNC79 and UNC80 are key regulators of the channel function. However, the behavioral effects of the channel complex are not entirely clear and the neurons in which the channel functions remain to be identified. In a forward genetic screen for C. elegans mutants with defective avoidance response to the plant hormone methyl salicylate (MeSa), we isolated multiple loss-of-function mutations in unc-80 and unc-79. C. elegans NALCN mutants exhibited similarly defective MeSa avoidance. Interestingly, NALCN, unc-80 and unc-79 mutants all showed wild type-like responses to other attractive or repelling odorants, suggesting that NALCN does not broadly affect odor detection or related forward and reversal behaviors. To understand in which neurons the channel functions, we determined the identities of a subset of unc-80-expressing neurons. We found that unc-79 and unc-80 are expressed and function in overlapping neurons, which verified previous assumptions. Neuron-specific transgene rescue and knockdown experiments suggest that the command interneurons AVA and AVE and the anterior guidepost neuron AVG can play a sufficient role in mediating unc-80 regulation of the MeSa avoidance. Though primarily based on genetic analyses, our results further imply that MeSa might activate NALCN by direct or indirect actions. Altogether, we provide an initial look into the key neurons in which the NALCN channel complex functions and identify a novel function of the channel in regulating C. elegans reversal behavior through command interneurons.

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