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https://www.readbyqxmd.com/read/29761896/sphingolipids-regulate-neuromuscular-synapse-structure-and-function-in-drosophila
#1
Ryan J H West, Laura Briggs, Maria Perona Fjeldstad, Richard R Ribchester, Sean T Sweeney
Sphingolipids are found in abundance at synapses and have been implicated in regulation of synapse structure, function and degeneration. Their precise role in these processes, however, remains obscure. Serine Palmitoyl-transferase (SPT) is the first enzymatic step for synthesis of sphingolipids. Analysis of the Drosophila larval neuromuscular junction revealed mutations in the SPT enzyme subunit, lace/SPTLC2 resulted in deficits in synaptic structure and function. Although neuromuscular junction (NMJ) length is normal in lace mutants, the number of boutons per NMJ is reduced to ∼50% of the wild type number...
May 15, 2018: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29742428/a-glutamate-homeostat-controls-the-presynaptic-inhibition-of-neurotransmitter-release
#2
Xiling Li, Pragya Goel, Joyce Wondolowski, Jeremy Paluch, Dion Dickman
We have interrogated the synaptic dialog that enables the bi-directional, homeostatic control of presynaptic efficacy at the glutamatergic Drosophila neuromuscular junction (NMJ). We find that homeostatic depression and potentiation use disparate genetic, induction, and expression mechanisms. Specifically, homeostatic potentiation is achieved through reduced CaMKII activity postsynaptically and increased abundance of active zone material presynaptically at one of the two neuronal subtypes innervating the NMJ, while homeostatic depression occurs without alterations in CaMKII activity and is expressed at both neuronal subtypes...
May 8, 2018: Cell Reports
https://www.readbyqxmd.com/read/29615874/structural-and-molecular-properties-of-insect-type-ii-motor-axon-terminals
#3
Bettina Stocker, Christina Bochow, Christine Damrau, Thomas Mathejczyk, Heike Wolfenberg, Julien Colomb, Claudia Weber, Niraja Ramesh, Carsten Duch, Natalia M Biserova, Stephan Sigrist, Hans-Joachim Pflüger
A comparison between the axon terminals of octopaminergic efferent dorsal or ventral unpaired median neurons in either desert locusts ( Schistocerca gregaria ) or fruit flies ( Drosophila melanogaster ) across skeletal muscles reveals many similarities. In both species the octopaminergic axon forms beaded fibers where the boutons or varicosities form type II terminals in contrast to the neuromuscular junction (NMJ) or type I terminals. These type II terminals are immunopositive for both tyramine and octopamine and, in contrast to the type I terminals, which possess clear synaptic vesicles, only contain dense core vesicles...
2018: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/29604258/novel-drosophila-model-for-mitochondrial-diseases-by-targeting-of-a-solute-carrier-protein-slc25a46
#4
Kojiro Suda, Ibuki Ueoka, Yumiko Azuma, Yuuka Muraoka, Hideki Yoshida, Masamitsu Yamaguchi
Mutations in SLC25A46 gene have been identified in mitochondrial diseases that are sometimes classified as Charcot-Marie-Tooth disease type 2, optic atrophy and Leigh syndrome. Human SLC25A46 functions as a transporter across the outer mitochondrial membrane. However, it is still unknown how the neurodegeneration occurring in these diseases relates to the loss of SLC25A46 function. Drosophila has CG5755 (dSLC25A46) as a single human SLC25A46 homolog. Here we established pan-neuron specific dSLC25A46 knockdown flies, and examined their phenotypes...
March 28, 2018: Brain Research
https://www.readbyqxmd.com/read/29528393/novel-insights-into-smaled2-bicd2-mutations-increase-microtubule-stability-and-cause-defects-in-axonal-and-nmj-development
#5
Lilian A Martinez Carrera, Elke Gabriel, Colin D Donohoe, Irmgard Hölker, Aruljothi Mariappan, Markus Storbeck, Mirka Uhlirova, Jay Gopalakrishnan, Brunhilde Wirth
Bicaudal D2 (BICD2) encodes a highly conserved motor adaptor protein that regulates the dynein-dynactin complex in different cellular processes. Heterozygous mutations in BICD2 cause autosomal dominant lower extremity-predominant spinal muscular atrophy-2 (SMALED2). Although, various BICD2 mutations have been shown to alter interactions with different binding partners or the integrity of the Golgi apparatus, the specific pathological effects of BICD2 mutations underlying SMALED2 remain elusive. Here, we show that the fibroblasts derived from individuals with SMALED2 exhibit stable microtubules...
May 15, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29520219/plexin-semaphorin-signaling-modifies-neuromuscular-defects-in-a-drosophila-model-of-peripheral-neuropathy
#6
Stuart J Grice, James N Sleigh, M Zameel Cader
Dominant mutations in GARS , encoding the ubiquitous enzyme glycyl-tRNA synthetase (GlyRS), cause peripheral nerve degeneration and Charcot-Marie-Tooth disease type 2D (CMT2D). This genetic disorder exemplifies a recurring paradigm in neurodegeneration, in which mutations in essential genes cause selective degeneration of the nervous system. Recent evidence suggests that the mechanism underlying CMT2D involves extracellular neomorphic binding of mutant GlyRS to neuronally-expressed proteins. Consistent with this, our previous studies indicate a non-cell autonomous mechanism, whereby mutant GlyRS is secreted and interacts with the neuromuscular junction (NMJ)...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29499182/glucuronylated-core-1-glycans-are-required-for-precise-localization-of-neuromuscular-junctions-and-normal-formation-of-basement-membranes-on-drosophila-muscles
#7
Kazuyoshi Itoh, Yoshihiro Akimoto, Shu Kondo, Tomomi Ichimiya, Kazuhiro Aoki, Michael Tiemeyer, Shoko Nishihara
T antigen (Galβ1-3GalNAcα1-Ser/Thr) is an evolutionary-conserved mucin-type core 1 glycan structure in animals synthesized by core 1 β1,3-galactosyltransferase 1 (C1GalT1). Previous studies showed that T antigen produced by Drosophila C1GalT1 (dC1GalT1) was expressed in various tissues and dC1GalT1 loss in larvae led to various defects, including decreased number of circulating hemocytes, hyper-differentiation of hematopoietic stem cells in lymph glands, malformation of the central nervous system, mislocalization of neuromuscular junction (NMJ) boutons, and ultrastructural abnormalities in NMJs and muscle cells...
April 15, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29464198/unraveling-synaptic-gcamp-signals-differential-excitability-and-clearance-mechanisms-underlying-distinct-ca-2-dynamics-in-tonic-and-phasic-excitatory-and-aminergic-modulatory-motor-terminals-in-drosophila
#8
Xiaomin Xing, Chun-Fang Wu
GCaMP is an optogenetic Ca2+ sensor widely used for monitoring neuronal activities but the precise physiological implications of GCaMP signals remain to be further delineated among functionally distinct synapses. The Drosophila neuromuscular junction (NMJ), a powerful genetic system for studying synaptic function and plasticity, consists of tonic and phasic glutamatergic and modulatory aminergic motor terminals of distinct properties. We report a first simultaneous imaging and electric recording study to directly contrast the frequency characteristics of GCaMP signals of the three synapses for physiological implications...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29411505/transcriptomics-of-aged-drosophila-motor-neurons-reveals-a-matrix-metalloproteinase-that-impairs-motor-function
#9
Jorge Azpurua, Rebekah E Mahoney, Benjamin A Eaton
The neuromuscular junction (NMJ) is responsible for transforming nervous system signals into motor behavior and locomotion. In the fruit fly Drosophila melanogaster, an age-dependent decline in motor function occurs, analogous to the decline experienced in mice, humans, and other mammals. The molecular and cellular underpinnings of this decline are still poorly understood. By specifically profiling the transcriptome of Drosophila motor neurons across age using custom microarrays, we found that the expression of the matrix metalloproteinase 1 (dMMP1) gene reproducibly increased in motor neurons in an age-dependent manner...
April 2018: Aging Cell
https://www.readbyqxmd.com/read/29378961/myopic-hd-ptp-ptpn23-selectively-regulates-synaptic-neuropeptide-release
#10
Dinara Bulgari, Anupma Jha, David L Deitcher, Edwin S Levitan
Neurotransmission is mediated by synaptic exocytosis of neuropeptide-containing dense-core vesicles (DCVs) and small-molecule transmitter-containing small synaptic vesicles (SSVs). Exocytosis of both vesicle types depends on Ca2+ and shared secretory proteins. Here, we show that increasing or decreasing expression of Myopic (mop, HD-PTP, PTPN23), a Bro1 domain-containing pseudophosphatase implicated in neuronal development and neuropeptide gene expression, increases synaptic neuropeptide stores at the Drosophila neuromuscular junction (NMJ)...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29373576/kinesin-khc-73-kif13b-modulates-retrograde-bmp-signaling-by-influencing-endosomal-dynamics-at-the-drosophila-neuromuscular-junction
#11
Edward H Liao, Lindsay Gray, Kazuya Tsurudome, Wassim El-Mounzer, Fatima Elazzouzi, Christopher Baim, Sarah Farzin, Mario R Calderon, Grant Kauwe, A Pejmun Haghighi
Retrograde signaling is essential for neuronal growth, function and survival; however, we know little about how signaling endosomes might be directed from synaptic terminals onto retrograde axonal pathways. We have identified Khc-73, a plus-end directed microtubule motor protein, as a regulator of sorting of endosomes in Drosophila larval motor neurons. The number of synaptic boutons and the amount of neurotransmitter release at the Khc-73 mutant larval neuromuscular junction (NMJ) are normal, but we find a significant decrease in the number of presynaptic release sites...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29317220/acamprosate-rescues-neuronal-defects-in-the-drosophila-model-of-fragile-x-syndrome
#12
Russell L Hutson, Rachel L Thompson, Andrew P Bantel, Charles R Tessier
AIMS: Several off-label studies have shown that acamprosate can provide some clinical benefits in youth with Fragile X Syndrome (FXS), an autism spectrum disorder caused by loss of function of the highly conserved FMR1 gene. This study investigated the ability of acamprosate to rescue cellular, molecular and behavioral defects in the Drosophila model of FXS. MAIN METHODS: A high (100μM) and low (10μM) dose of acamprosate was fed to Drosophila FXS (dfmr1 null) or genetic control (w1118 ) larvae and then analyzed in multiple paradigms...
February 15, 2018: Life Sciences
https://www.readbyqxmd.com/read/29282074/the-rap-activator-gef26-regulates-synaptic-growth-and-neuronal-survival-via-inhibition-of-bmp-signaling
#13
Keunjung Heo, Minyeop Nahm, Min-Jung Lee, Young-Eun Kim, Chang-Seok Ki, Seung Hyun Kim, Seungbok Lee
In Drosophila, precise regulation of BMP signaling is essential for normal synaptic growth at the larval neuromuscular junction (NMJ) and neuronal survival in the adult brain. However, the molecular mechanisms underlying fine-tuning of BMP signaling in neurons remain poorly understood. We show that loss of the Drosophila PDZ guanine nucleotide exchange factor Gef26 significantly increases synaptic growth at the NMJ and enhances BMP signaling in motor neurons. We further show that Gef26 functions upstream of Rap1 in motor neurons to restrain synaptic growth...
December 28, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29258853/drosophila-active-zones-from-molecules-to-behaviour
#14
REVIEW
Nadine Ehmann, David Owald, Robert J Kittel
In a constantly changing environment, neuronal circuits need to be updated and adjusted to elicit directed actions. Synaptic plasticity plays an important role in modulating such globally and locally acting networks. The active zone (AZ) is a protein-rich compartment of chemical synapses, where precisely orchestrated molecular interactions control synaptic vesicle (SV) fusion with the presynaptic membrane. The subsequent release of neurotransmitter substances onto postsynaptic receptor fields forms the basis of neuronal communication...
February 2018: Neuroscience Research
https://www.readbyqxmd.com/read/29249293/epigenetic-crosstalk-pharmacological-inhibition-of-hdacs-can-rescue-defective-synaptic-morphology-and-neurotransmission-phenotypes-associated-with-loss-of-the-chromatin-reader-kismet
#15
REVIEW
Nina K Latcheva, Jennifer M Viveiros, Edward A Waddell, Phuong T T Nguyen, Faith L W Liebl, Daniel R Marenda
We are beginning to appreciate the complex mechanisms by which epigenetic proteins control chromatin dynamics to tightly regulate normal development. However, the interaction between these proteins, particularly in the context of neuronal function, remains poorly understood. Here, we demonstrate that the activity of histone deacetylases (HDACs) opposes that of a chromatin remodeling enzyme at the Drosophila neuromuscular junction (NMJ). Pharmacological inhibition of HDAC function reverses loss of function phenotypes associated with Kismet, a chromodomain helicase DNA-binding (CHD) protein...
March 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29217522/-drosophila-syd-1-has-rhogap-activity-that-is-required-for-presynaptic-clustering-of-bruchpilot-elks-but-not-neurexin-1
#16
Michael A Spinner, David A Walla, Tory G Herman
Syd-1 proteins are required for presynaptic development in worm, fly, and mouse. Syd-1 proteins in all three species contain a Rho GTPase activating protein (GAP)-like domain of unclear significance: invertebrate Syd-1s are thought to lack GAP activity, and mouse mSYD1A has GAP activity that is thought to be dispensable for its function. Here, we show that Drosophila melanogaster Syd-1 can interact with all six fly Rhos and has GAP activity toward Rac1 and Cdc42. During development, fly Syd-1 clusters multiple presynaptic proteins at the neuromuscular junction (NMJ), including the cell adhesion molecule Neurexin (Nrx-1) and the active zone (AZ) component Bruchpilot (Brp), both of which Syd-1 binds directly...
February 2018: Genetics
https://www.readbyqxmd.com/read/29161404/mutation-dependent-aggregation-and-toxicity-in-a-drosophila-model-for-ubqln2-associated-als
#17
Sang Hwa Kim, Shannon G Stiles, Joseph M Feichtmeier, Nandini Ramesh, Lihong Zhan, Mark A Scalf, Lloyd M Smith, Udai Bhan Pandey, Randal S Tibbetts
Members of the conserved ubiquilin (UBQLN) family of ubiquitin (Ub) chaperones harbor an antipodal UBL (Ub-like)-UBA (Ub-associated) domain arrangement and participate in proteasome and autophagosome-mediated protein degradation. Mutations in a proline-rich-repeat region (PRR) of UBQLN2 cause amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD); however, neither the normal functions of the PRR nor impacts of ALS-associated mutations within it are well understood. In this study, we show that ALS mutations perturb UBQLN2 solubility and folding in a mutation-specific manner...
January 15, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29130196/super-resolution-single-molecule-fish-at-the-drosophila-neuromuscular-junction
#18
Joshua S Titlow, Lu Yang, Richard M Parton, Ana Palanca, Ilan Davis
The lack of an effective, simple, and highly sensitive protocol for fluorescent in situ hybridization (FISH) at the Drosophila larval neuromuscular junction (NMJ) has hampered the study of mRNA biology. Here, we describe our modified single molecule FISH (smFISH) methods that work well in whole mount Drosophila NMJ preparations to quantify primary transcription and count individual cytoplasmic mRNA molecules in specimens while maintaining ultrastructural preservation. The smFISH method is suitable for high-throughput sample processing and 3D image acquisition using any conventional microscopy imaging modality and is compatible with the use of antibody colabeling and transgenic fluorescent protein tags in axons, glia, synapses, and muscle cells...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29114039/neuronal-activity-drives-fmrp-and-hspg-dependent-matrix-metalloproteinase-function-required-for-rapid-synaptogenesis
#19
Mary L Dear, Jarrod Shilts, Kendal Broadie
Matrix metalloproteinase (MMP) functions modulate synapse formation and activity-dependent plasticity. Aberrant MMP activity is implicated in fragile X syndrome (FXS), a disease caused by the loss of the RNA-binding protein FMRP and characterized by neurological dysfunction and intellectual disability. Gene expression studies in Drosophila suggest that Mmps cooperate with the heparan sulfate proteoglycan (HSPG) glypican co-receptor Dally-like protein (Dlp) to restrict trans-synaptic Wnt signaling and that synaptogenic defects in the fly model of FXS are alleviated by either inhibition of Mmp or genetic reduction of Dlp...
November 7, 2017: Science Signaling
https://www.readbyqxmd.com/read/29105522/orb2-as-modulator-of-brat-and-their-role-at-the-neuromuscular-junction
#20
Elena Santana, Sergio Casas-Tintó
How synapses are built and dismantled is a central question in neurobiology. A wide range of proteins and processes from gene transcription to protein degradation are involved. Orb2 regulates mRNA translation depending on its monomeric or oligomeric state to modulate nervous system development and memory. Orb2 is expressed in Drosophila larval brain and neuromuscular junction (NMJ), Orb2 knockdown causes a reduction of synapse number and defects in neuronal morphology. Brain tumor (Brat) is an Orb2 target; it is expressed in larval brain related with cell growth and proliferation...
December 2017: Journal of Neurogenetics
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