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https://www.readbyqxmd.com/read/27770767/mical-like-regulates-fasciclin-ii-membrane-cycling-and-synaptic-development
#1
Minyeop Nahm, Sunyoung Park, Jihye Lee, Seungbok Lee
Fasciclin II (FasII), the Drosophila ortholog of neural cell adhesion molecule (NCAM), plays a critical role in synaptic stabilization and plasticity. Although this molecule undergoes constitutive cycling at the synaptic membrane, how its membrane trafficking is regulated to ensure proper synaptic development remains poorly understood. In a genetic screen, we recovered a mutation in Drosophila mical-like that displays an increase in bouton numbers and a decrease in FasII levels at the neuromuscular junction (NMJ)...
October 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27736876/dbo-henji-modulates-synaptic-dpak-to-gate-glutamate-receptor-abundance-and-postsynaptic-response
#2
Manyu Wang, Pei-Yi Chen, Chien-Hsiang Wang, Tzu-Ting Lai, Pei-I Tsai, Ying-Ju Cheng, Hsiu-Hua Kao, Cheng-Ting Chien
In response to environmental and physiological changes, the synapse manifests plasticity while simultaneously maintains homeostasis. Here, we analyzed mutant synapses of henji, also known as dbo, at the Drosophila neuromuscular junction (NMJ). In henji mutants, NMJ growth is defective with appearance of satellite boutons. Transmission electron microscopy analysis indicates that the synaptic membrane region is expanded. The postsynaptic density (PSD) houses glutamate receptors GluRIIA and GluRIIB, which have distinct transmission properties...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27711243/cgmp-dependent-protein-kinase-inhibition-extends-the-upper-temperature-limit-of-stimulus-evoked-calcium-responses-in-motoneuronal-boutons-of-drosophila-melanogaster-larvae
#3
Jennifer L Krill, Ken Dawson-Scully
While the mammalian brain functions within a very narrow range of oxygen concentrations and temperatures, the fruit fly, Drosophila melanogaster, has employed strategies to deal with a much wider range of acute environmental stressors. The foraging (for) gene encodes the cGMP-dependent protein kinase (PKG), has been shown to regulate thermotolerance in many stress-adapted species, including Drosophila, and could be a potential therapeutic target in the treatment of hyperthermia in mammals. Whereas previous thermotolerance studies have looked at the effects of PKG variation on Drosophila behavior or excitatory postsynaptic potentials at the neuromuscular junction (NMJ), little is known about PKG effects on presynaptic mechanisms...
2016: PloS One
https://www.readbyqxmd.com/read/27567686/presynaptic-camkii-regulates-activity-dependent-axon-terminal-growth
#4
Katherine R Nesler, Emily L Starke, Nathan G Boin, Matthew Ritz, Scott A Barbee
Spaced synaptic depolarization induces rapid axon terminal growth and the formation of new synaptic boutons at the Drosophila larval neuromuscular junction (NMJ). Here, we identify a novel presynaptic function for the Calcium/Calmodulin-dependent Kinase II (CamKII) protein in the control of activity-dependent synaptic growth. Consistent with this function, we find that both total and phosphorylated CamKII (p-CamKII) are enriched in axon terminals. Interestingly, p-CamKII appears to be enriched at the presynaptic axon terminal membrane...
October 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27535427/role-of-bmp-receptor-traffic-in-synaptic-growth-defects-in-an-als-model
#5
Mugdha Deshpande, Zachary Feiger, Amanda K Shilton, Christina C Luo, Ethan Silverman, Avital A Rodal
TAR DNA-binding protein 43 (TDP-43) is genetically and functionally linked to amyotrophic lateral sclerosis (ALS) and regulates transcription, splicing, and transport of thousands of RNA targets that function in diverse cellular pathways. In ALS, pathologically altered TDP-43 is believed to lead to disease by toxic gain-of-function effects on RNA metabolism, as well as by sequestering endogenous TDP-43 and causing its loss of function. However, it is unclear which of the numerous cellular processes disrupted downstream of TDP-43 dysfunction lead to neurodegeneration...
October 1, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27466186/coordinated-movement-neuromuscular-synaptogenesis-and-trans-synaptic-signaling-defects-in-drosophila-galactosemia-models
#6
Patricia P Jumbo-Lucioni, William M Parkinson, Danielle L Kopke, Kendal Broadie
The multiple galactosemia disease states manifest long-term neurological symptoms. Galactosemia I results from loss of galactose-1-phosphate uridyltransferase (GALT), which converts galactose-1-phosphate + UDP-glucose to glucose-1-phosphate + UDP-galactose. Galactosemia II results from loss of galactokinase (GALK), phosphorylating galactose to galactose-1-phosphate. Galactosemia III results from the loss of UDP-galactose 4'-epimerase (GALE), which interconverts UDP-galactose and UDP-glucose, as well as UDP-N-acetylgalactosamine and UDP-N-acetylglucosamine...
July 27, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27459966/the-influence-of-postsynaptic-structure-on-missing-quanta-at-the-drosophila-neuromuscular-junction
#7
Christine T Nguyen, Bryan A Stewart
BACKGROUND: Synaptic transmission requires both pre- and post-synaptic elements for neural communication. The postsynaptic structure contributes to the ability of synaptic currents to induce voltage changes in postsynaptic cells. At the Drosophila neuromuscular junction (NMJ), the postsynaptic structure, known as the subsynaptic reticulum (SSR), consists of elaborate membrane folds that link the synaptic contacts to the muscle, but its role in synaptic physiology is poorly understood...
2016: BMC Neuroscience
https://www.readbyqxmd.com/read/27232889/angelman-syndrome-protein-ube3a-regulates-synaptic-growth-and-endocytosis-by-inhibiting-bmp-signaling-in-drosophila
#8
Wenhua Li, Aiyu Yao, Hui Zhi, Kuldeep Kaur, Yong-Chuan Zhu, Mingyue Jia, Hui Zhao, Qifu Wang, Shan Jin, Guoli Zhao, Zhi-Qi Xiong, Yong Q Zhang
Altered expression of the E3 ubiquitin ligase UBE3A, which is involved in protein degradation through the proteasome-mediated pathway, is associated with neurodevelopmental and behavioral defects observed in Angelman syndrome (AS) and autism. However, little is known about the neuronal function of UBE3A and the pathogenesis of UBE3A-associated disorders. To understand the in vivo function of UBE3A in the nervous system, we generated multiple mutations of ube3a, the Drosophila ortholog of UBE3A. We found a significantly increased number of total boutons and satellite boutons in conjunction with compromised endocytosis in the neuromuscular junctions (NMJs) of ube3a mutants compared to the wild type...
May 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27213489/why-quantification-matters-characterization-of-phenotypes-at-the-drosophila-larval-neuromuscular-junction
#9
Mario Sanhueza, Anisha Kubasik-Thayil, Giuseppa Pennetta
Most studies on morphogenesis rely on qualitative descriptions of how anatomical traits are affected by the disruption of specific genes and genetic pathways. Quantitative descriptions are rarely performed, although genetic manipulations produce a range of phenotypic effects and variations are observed even among individuals within control groups. Emerging evidence shows that morphology, size and location of organelles play a previously underappreciated, yet fundamental role in cell function and survival. Here we provide step-by-step instructions for performing quantitative analyses of phenotypes at the Drosophila larval neuromuscular junction (NMJ)...
2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27197982/human-senataxin-modulates-structural-plasticity-of-the-neuromuscular-junction-in-drosophila-through-a-neuronally-conserved-tgf%C3%AE-signalling-pathway
#10
Zeeshan Mushtaq, Saumitra Dey Choudhury, Sri Krishna Gangwar, Genny Orso, Vimlesh Kumar
BACKGROUND: Mutations in the human Senataxin (hSETX) gene have been shown to cause two forms of neurodegenerative disorders - a dominant form called amyotrophic lateral sclerosis type 4 (ALS4) and a recessive form called ataxia with oculomotor apraxia type 2 (AOA2). SETX is a putative DNA/RNA helicase involved in RNA metabolism. Although several dominant mutations linked with ALS4 have been identified in SETX, their contribution towards ALS4 pathophysiology is still elusive. METHOD: In order to model ALS4 in Drosophila and to elucidate the morphological, physiological and signalling consequences, we overexpressed the wild-type and pathological forms of hSETX in Drosophila...
2016: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/27022630/rab3-gef-controls-active-zone-development-at-the-drosophila-neuromuscular-junction
#11
Haneui Bae, Shirui Chen, John P Roche, Minrong Ai, Chunlai Wu, Aaron Diantonio, Ethan R Graf
Synaptic signaling involves the release of neurotransmitter from presynaptic active zones (AZs). Proteins that regulate vesicle exocytosis cluster at AZs, composing the cytomatrix at the active zone (CAZ). At the Drosophila neuromuscular junction (NMJ), the small GTPase Rab3 controls the distribution of CAZ proteins across release sites, thereby regulating the efficacy of individual AZs. Here we identify Rab3-GEF as a second protein that acts in conjunction with Rab3 to control AZ protein composition. At rab3-GEF mutant NMJs, Bruchpilot (Brp) and Ca(2+) channels are enriched at a subset of AZs, leaving the remaining sites devoid of key CAZ components in a manner that is indistinguishable from rab3 mutant NMJs...
March 2016: ENeuro
https://www.readbyqxmd.com/read/26998933/a-new-fiji-based-algorithm-that-systematically-quantifies-nine-synaptic-parameters-provides-insights-into-drosophila-nmj-morphometry
#12
Bonnie Nijhof, Anna Castells-Nobau, Louis Wolf, Jolanda M Scheffer-de Gooyert, Ignacio Monedero, Laura Torroja, Lluis Coromina, Jeroen A W M van der Laak, Annette Schenck
The morphology of synapses is of central interest in neuroscience because of the intimate relation with synaptic efficacy. Two decades of gene manipulation studies in different animal models have revealed a repertoire of molecules that contribute to synapse development. However, since such studies often assessed only one, or at best a few, morphological features at a given synapse, it remained unaddressed how different structural aspects relate to one another. Furthermore, such focused and sometimes only qualitative approaches likely left many of the more subtle players unnoticed...
March 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/26987116/the-extracellular-and-cytoplasmic-domains-of-syndecan-cooperate-postsynaptically-to-promote-synapse-growth-at-the-drosophila-neuromuscular-junction
#13
Margaret U Nguyen, Jereen Kwong, Julia Chang, Victoria G Gillet, Rachel M Lee, Karl Gregory Johnson
The heparan sulfate proteoglycan (HSPG) Syndecan (Sdc) is a crucial regulator of synapse development and growth in both vertebrates and invertebrates. In Drosophila, Sdc binds via its extracellular heparan sulfate (HS) sidechains to the receptor protein tyrosine phosphatase LAR to promote the morphological growth of the neuromuscular junction (NMJ). To date, however, little else is known about the molecular mechanisms by which Sdc functions to promote synapse growth. Here we show that all detectable Sdc found at the NMJ is provided by the muscle, strongly suggesting a post-synaptic role for Sdc...
2016: PloS One
https://www.readbyqxmd.com/read/26940433/synaptic-roles-for-phosphomannomutase-type-2-in-a-new-drosophila-congenital-disorder-of-glycosylation-disease-model
#14
William M Parkinson, Michelle Dookwah, Mary Lynn Dear, Cheryl L Gatto, Kazuhiro Aoki, Michael Tiemeyer, Kendal Broadie
Congenital disorders of glycosylation (CDGs) constitute a rapidly growing family of human diseases resulting from heritable mutations in genes driving the production and modification of glycoproteins. The resulting symptomatic hypoglycosylation causes multisystemic defects that include severe neurological impairments, revealing a particularly critical requirement for tightly regulated glycosylation in the nervous system. The most common CDG, CDG-Ia (PMM2-CDG), arises from phosphomannomutase type 2 (PMM2) mutations...
May 1, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/26924931/drosophila-homolog-of-human-kif22-at-the-autism-linked-16p11-2-loci-influences-synaptic-connectivity-at-larval-neuromuscular-junctions
#15
Sang Mee Park, J Troy Littleton, Hae Ryoun Park, Ji Hye Lee
Copy number variations at multiple chromosomal loci, including 16p11.2, have recently been implicated in the pathogenesis of autism spectrum disorder (ASD), a neurodevelopmental disease that affects 1~3% of children worldwide. The aim of this study was to investigate the roles of human genes at the 16p11.2 loci in synaptic development using Drosophila larval neuromuscular junctions (NMJ), a well-established model synapse with stereotypic innervation patterns. We conducted a preliminary genetic screen based on RNA interference in combination with the GAL4-UAS system, followed by mutational analyses...
February 2016: Experimental Neurobiology
https://www.readbyqxmd.com/read/26920756/%C3%AF-2-adaptin-facilitates-basal-synaptic-transmission-and-is-required-for-regenerating-endo-exo-cycling-pool-under-high-frequency-nerve-stimulation-in-drosophila
#16
Saumitra Dey Choudhury, Zeeshan Mushtaq, Suneel Reddy-Alla, Sruthi S Balakrishnan, Rajan S Thakur, Kozhalmannom S Krishnan, Padinjat Raghu, Mani Ramaswami, Vimlesh Kumar
The functional requirement of adapter protein 2 (AP2) complex in synaptic membrane retrieval by clathrin-mediated endocytosis is not fully understood. Here we isolated and functionally characterized a mutation that dramatically altered synaptic development. Based on the aberrant neuromuscular junction (NMJ) synapse, we named this mutation angur (a Hindi word meaning "grapes"). Loss-of-function alleles of angur show more than twofold overgrowth in bouton numbers and a dramatic decrease in bouton size. We mapped the angur mutation to σ2-adaptin, the smallest subunit of the AP2 complex...
May 2016: Genetics
https://www.readbyqxmd.com/read/26902497/tbph-tdp-43-modulates-translation-of-drosophila-futsch-mrna-through-an-ug-rich-sequence-within-its-5-utr
#17
Maurizio Romano, Fabian Feiguin, Emanuele Buratti
Nuclear factor TDP-43 is an evolutionarily conserved multifunctional RNA-binding protein associated with frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). In recent years, Drosophila models of ALS based on TDP-43 knockdown/overexpression have allowed to find several connections with disease. Among these, we have previously described that silencing the expression of its fly ortholog (TBPH) can alter the expression of the neuronal microtubule-associated protein Futsch leading to alterations of neuromuscular junction (NMJ) organization...
September 15, 2016: Brain Research
https://www.readbyqxmd.com/read/26901416/c-terminal-src-kinase-gates-homeostatic-synaptic-plasticity-and-regulates-fasciclin-ii-expression-at-the-drosophila-neuromuscular-junction
#18
Ashlyn M Spring, Douglas J Brusich, C Andrew Frank
Forms of homeostatic plasticity stabilize neuronal outputs and promote physiologically favorable synapse function. A well-studied homeostatic system operates at the Drosophila melanogaster larval neuromuscular junction (NMJ). At the NMJ, impairment of postsynaptic glutamate receptor activity is offset by a compensatory increase in presynaptic neurotransmitter release. We aim to elucidate how this process operates on a molecular level and is preserved throughout development. In this study, we identified a tyrosine kinase-driven signaling system that sustains homeostatic control of NMJ function...
February 2016: PLoS Genetics
https://www.readbyqxmd.com/read/26858605/adducin-at-the-neuromuscular-junction-in-amyotrophic-lateral-sclerosis-hanging-on-for-dear-life
#19
REVIEW
Charles Krieger, Simon Ji Hau Wang, Soo Hyun Yoo, Nicholas Harden
The neurological dysfunction in amyotrophic lateral sclerosis (ALS)/motor neurone disease (MND) is associated with defective nerve-muscle contacts early in the disease suggesting that perturbations of cell adhesion molecules (CAMs) linking the pre- and post-synaptic components of the neuromuscular junction (NMJ) are involved. To search for candidate proteins implicated in this degenerative process, researchers have studied the Drosophila larval NMJ and find that the cytoskeleton-associated protein, adducin, is ideally placed to regulate synaptic contacts...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/26815659/a-novel-noncanonical-bmp-pathway-modulates-synapse-maturation-at-the-drosophila-neuromuscular-junction
#20
Mikolaj J Sulkowski, Tae Hee Han, Carolyn Ott, Qi Wang, Esther M Verheyen, Jennifer Lippincott-Schwartz, Mihaela Serpe
At the Drosophila NMJ, BMP signaling is critical for synapse growth and homeostasis. Signaling by the BMP7 homolog, Gbb, in motor neurons triggers a canonical pathway-which modulates transcription of BMP target genes, and a noncanonical pathway-which connects local BMP/BMP receptor complexes with the cytoskeleton. Here we describe a novel noncanonical BMP pathway characterized by the accumulation of the pathway effector, the phosphorylated Smad (pMad), at synaptic sites. Using genetic epistasis, histology, super resolution microscopy, and electrophysiology approaches we demonstrate that this novel pathway is genetically distinguishable from all other known BMP signaling cascades...
January 2016: PLoS Genetics
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