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https://www.readbyqxmd.com/read/28912273/neuroligin-4-regulates-synaptic-growth-via-the-bone-morphogenetic-protein-bmp-signaling-pathway-at-the-drosophila-neuromuscular-junction
#1
Xinwang Zhang, Menglong Rui, Guangmin Gan, Cong Huang, Jukang Yi, Huihui Lv, Wei Xie
The neuroligin (Nlg) family of neural cell adhesion molecules is thought to be required for synapse formation and development, and has been linked to the development of autism spectrum disorders in humans. In Drosophila melanogaster, mutations in the neuroligin 1-3 genes have been reported to induce synapse developmental defects at neuromuscular junctions (NMJs), but the role of neuroligin 4 (dnlg4) in synapse development has not been determined. Here, we report that the Drosophila neuroligin 4 (DNlg4) is different from DNlg1-3 that it presynaptically regulates NMJ synapse development...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28860114/notum-coordinates-synapse-development-via-extracellular-regulation-of-wnt-wingless-trans-synaptic-signaling
#2
Danielle L Kopke, Sofia C Lima, Cyrille Alexandre, Kendal Broadie
Synaptogenesis requires orchestrated communication between pre- and postsynaptic cells via coordinated trans-synaptic signaling across the extracellular synaptomatrix. The first discovered Wnt signaling ligand Drosophila Wingless (Wg; Wnt-1 in mammals) plays critical roles in synaptic development, regulating synapse architecture as well as functional differentiation. Here, we investigate synaptogenic functions of the secreted extracellular deacylase Notum, which restricts Wg signaling by cleaving an essential palmitoleate moiety...
August 31, 2017: Development
https://www.readbyqxmd.com/read/28846707/kek-6-a-truncated-trk-like-receptor-for-drosophila-neurotrophin-2-regulates-structural-synaptic-plasticity
#3
Suzana Ulian-Benitez, Simon Bishop, Istvan Foldi, Jill Wentzell, Chinenye Okenwa, Manuel G Forero, Bangfu Zhu, Marta Moreira, Mark Phizacklea, Graham McIlroy, Guiyi Li, Nicholas J Gay, Alicia Hidalgo
Neurotrophism, structural plasticity, learning and long-term memory in mammals critically depend on neurotrophins binding Trk receptors to activate tyrosine kinase (TyrK) signaling, but Drosophila lacks full-length Trks, raising the question of how these processes occur in the fly. Paradoxically, truncated Trk isoforms lacking the TyrK predominate in the adult human brain, but whether they have neuronal functions independently of full-length Trks is unknown. Drosophila has TyrK-less Trk-family receptors, encoded by the kekkon (kek) genes, suggesting that evolutionarily conserved functions for this receptor class may exist...
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28790398/shedding-light-on-alzheimer-s-%C3%AE-amyloidosis-photosensitized-methylene-blue-inhibits-self-assembly-of-%C3%AE-amyloid-peptides-and-disintegrates-their-aggregates
#4
Byung Il Lee, Yoon Seok Suh, You Jung Chung, Kweon Yu, Chan Beum Park
Abnormal aggregation of β-amyloid (Aβ) peptides is a major hallmark of Alzheimer's disease (AD). In spite of numerous attempts to prevent the β-amyloidosis, no effective drugs for treating AD have been developed to date. Among many candidate chemicals, methylene blue (MB) has proved its therapeutic potential for AD in a number of in vitro and in vivo studies; but the result of recent clinical trials performed with MB and its derivative was negative. Here, with the aid of multiple photochemical analyses, we first report that photoexcited MB molecules can block Aβ42 aggregation in vitro...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28745645/a-simple-neuronal-mechanical-injury-methodology-to-study-drosophila-motor-neuron-degeneration
#5
Erika B Danella, Lani C Keller
The degeneration of neurons occurs during normal development and in response to injury, stress, and disease. The cellular hallmarks of neuronal degeneration are remarkably similar in humans and invertebrates as are the molecular mechanisms that drive these processes. The fruit fly, Drosophila melanogaster, provides a powerful yet simple genetic model organism to study the cellular complexities of neurodegenerative diseases. In fact, approximately 70% of disease-associated human genes have a Drosophila homolog and a plethora of tools and assays have been described using flies to study human neurodegenerative diseases...
July 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28576972/secreted-tissue-inhibitor-of-matrix-metalloproteinase-restricts-trans-synaptic-signaling-to-coordinate-synaptogenesis
#6
Jarrod Shilts, Kendal Broadie
Synaptogenesis is coordinated by trans-synaptic signals that traverse the specialized synaptomatrix between presynaptic and postsynaptic cells. Matrix metalloproteinase (Mmp) activity sculpts this environment, balanced by secreted tissue inhibitors of Mmp (Timp). Here, we use the simplified Drosophila melanogaster matrix metalloproteome to test the consequences of eliminating all Timp regulatory control of Mmp activity at the neuromuscular junction (NMJ). Using in situ zymography, we find Timp limits Mmp activity at the NMJ terminal and shapes extracellular proteolytic dynamics surrounding individual synaptic boutons...
July 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28544556/electrophysiological-analysis-of-synaptic-transmission-in-drosophila
#7
REVIEW
Maria Bykhovskaia, Alexander Vasin
Synaptic transmission is dynamic, plastic, and highly regulated. Drosophila is an advantageous model system for genetic and molecular studies of presynaptic and postsynaptic mechanisms and plasticity. Electrical recordings of synaptic responses represent a wide-spread approach to study neuronal signaling and synaptic transmission. We discuss experimental techniques that allow monitoring synaptic transmission in Drosophila neuromuscular and central systems. Recordings of synaptic potentials or currents at the larval neuromuscular junction (NMJ) are most common and provide numerous technical advantages due to robustness of the preparation, large and identifiable muscles, and synaptic boutons which can be readily visualized...
September 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28520784/presynaptic-a%C3%AE-40-prevents-synapse-addition-in-the-adult-drosophila-neuromuscular-junction
#8
Begoña López-Arias, Enrique Turiégano, Ignacio Monedero, Inmaculada Canal, Laura Torroja
Complexity in the processing of the Amyloid Precursor Protein, which generates a mixture of βamyloid peptides, lies beneath the difficulty in understanding the etiology of Alzheimer's disease. Moreover, whether Aβ peptides have any physiological role in neurons is an unresolved question. By expressing single, defined Aβ peptides in Drosophila, specific effects can be discriminated in vivo. Here, we show that in the adult neuromuscular junction (NMJ), presynaptic expression of Aβ40 hinders the synaptic addition that normally occurs in adults, yielding NMJs with an invariable number of active zones at all ages tested...
2017: PloS One
https://www.readbyqxmd.com/read/28518121/two-algorithms-for-high-throughput-and-multi-parametric-quantification-of-drosophila-neuromuscular-junction-morphology
#9
Anna Castells-Nobau, Bonnie Nijhof, Ilse Eidhof, Louis Wolf, Jolanda M Scheffer-de Gooyert, Ignacio Monedero, Laura Torroja, Jeroen A W M van der Laak, Annette Schenck
Synaptic morphology is tightly related to synaptic efficacy, and in many cases morphological synapse defects ultimately lead to synaptic malfunction. The Drosophila larval neuromuscular junction (NMJ), a well-established model for glutamatergic synapses, has been extensively studied for decades. Identification of mutations causing NMJ morphological defects revealed a repertoire of genes that regulate synapse development and function. Many of these were identified in large-scale studies that focused on qualitative approaches to detect morphological abnormalities of the Drosophila NMJ...
May 3, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28500055/rnai-mediated-reverse-genetic-screen-identified-drosophila-chaperones-regulating-eye-and-neuromuscular-junction-morphology
#10
Sandeep Raut, Bhagaban Mallik, Arpan Parichha, Valsakumar Amrutha, Chandan Sahi, Vimlesh Kumar
Accumulation of toxic proteins in neurons has been linked with the onset of neurodegenerative diseases, which in many cases are characterized by altered neuronal function and synapse loss. Molecular chaperones help protein folding and the resolubilization of unfolded proteins, thereby reducing the protein aggregation stress. While most of the chaperones are expressed in neurons, their functional relevance remains largely unknown. Here, using bioinformatics analysis, we identified 95 Drosophila chaperones and classified them into seven different classes...
July 5, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28466185/tissue-specific-transcription-of-the-neuronal-gene-lim3-affects-drosophila-melanogaster-lifespan-and-locomotion
#11
Olga Y Rybina, Svetlana V Sarantseva, Ekaterina R Veselkina, Olga I Bolschakova, Alexander V Symonenko, Anna V Krementsova, Elena V Ryabova, Natalia V Roshina, Elena G Pasyukova
The identity of neuronal cell types is established and maintained by the expression of neuronal genes coding for ion channels, neurotransmitters, and neuropeptides, among others. Some of these genes have been shown to affect lifespan; however, their role in lifespan control remains largely unclear. The Drosophila melanogaster gene Lim3 encodes a transcription factor involved in complicated motor neuron specification networks. We previously identified Lim3 as a candidate gene affecting lifespan. To obtain direct evidence of the involvement of Lim3 in lifespan control, Lim3 overexpression and RNAi knockdown were induced in the nervous system and muscles of Drosophila using the GAL4-UAS binary system...
May 2, 2017: Biogerontology
https://www.readbyqxmd.com/read/28455372/regulation-of-neuromuscular-junction-organization-by-rab2-and-its-effector-ica69-in-drosophila
#12
Bhagaban Mallik, Manish Kumar Dwivedi, Zeeshan Mushtaq, Manisha Kumari, Praveen Kumar Verma, Vimlesh Kumar
The mechanisms underlying synaptic differentiation, which involves neuronal membrane and cytoskeletal remodeling, are not completely understood. We performed a targeted RNAi-mediated screen of Drosophila BAR-domain proteins and identified islet cell autoantigen 69 kDa (ICA69) as one of the key regulators of morphological differentiation of the larval neuromuscular junction (NMJ). We show that Drosophila ICA69 colocalizes with α-Spectrin at the NMJ. The conserved N-BAR domain of ICA69 deforms liposomes in vitro Full-length ICA69 and the ICAC but not the N-BAR domain of ICA69 induce filopodia in cultured cells...
June 1, 2017: Development
https://www.readbyqxmd.com/read/28379367/a-drosophila-model-of-als-reveals-a-partial-loss-of-function-of-causative-human-pfn1-mutants
#13
Chi-Hong Wu, Anthony Giampetruzzi, Helene Tran, Claudia Fallini, Fen-Biao Gao, John E Landers
Mutations in the profilin 1 (PFN1) gene are causative for familial amyotrophic lateral sclerosis (fALS). However, it is still not fully understood how these mutations lead to neurodegeneration. To address this question, we generated a novel Drosophila model expressing human wild-type and ALS-causative PFN1 mutants. We show that at larval neuromuscular junctions (NMJ), motor neuron expression of wild-type human PFN1 increases the number of ghost boutons, active zone density, F-actin content, and the formation of filopodia...
June 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28286469/the-ih-channel-gene-promotes-synaptic-transmission-and-coordinated-movement-in-drosophila-melanogaster
#14
Andrew P Hegle, C Andrew Frank, Anthony Berndt, Markus Klose, Douglas W Allan, Eric A Accili
Hyperpolarization-activated cyclic nucleotide-gated "HCN" channels, which underlie the hyperpolarization-activated current (Ih), have been proposed to play diverse roles in neurons. The presynaptic HCN channel is thought to both promote and inhibit neurotransmitter release from synapses, depending upon its interactions with other presynaptic ion channels. In larvae of Drosophila melanogaster, inhibition of the presynaptic HCN channel by the drug ZD7288 reduces the enhancement of neurotransmitter release at motor terminals by serotonin but this drug has no effect on basal neurotransmitter release, implying that the channel does not contribute to firing under basal conditions...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28256749/increased-postsynaptic-ca-2-reduces-mini-frequency-at-the-drosophila-larval-nmj
#15
Andrew S Powers, Jeffrey Grizzaffi, Gregory A Lnenicka
No abstract text is available yet for this article.
March 3, 2017: Synapse
https://www.readbyqxmd.com/read/28245518/altered-translational-repression-of-an-rna-binding-protein-elav-by-aoa2-causative-senataxin-mutation
#16
Saumitra Dey Choudhury, Ancy Vs, Zeeshan Mushtaq, Vimlesh Kumar
Mutations in Senataxin (SETX) gene causes two types of neurological disorders, Amyotrophic Lateral Sclerosis (ALS4) and Ataxia with Oculomotor Apraxia type 2 (AOA2). Recent studies in cultured cells suggest that SETX plays a crucial role at the interface of transcription and the DNA damage response. Whether SETX can alter translational of specific RNA is not known. In this study, we report that expressing AOA2-causative truncated form of human SETX in Drosophila neurons alters the development of neuromuscular junction (NMJ) synapses...
February 28, 2017: Synapse
https://www.readbyqxmd.com/read/28213447/the-drosophila-postsynaptic-deg-enac-channel-ppk29-contributes-to-excitatory-neurotransmission
#17
Alexis Hill, Xingguo Zheng, Xiling Li, Ross McKinney, Dion Dickman, Yehuda Ben-Shahar
The protein family of degenerin/epithelial sodium channels (DEG/ENaCs) is composed of diverse animal-specific, non-voltage-gated ion channels that play important roles in regulating cationic gradients across epithelial barriers. Some family members are also enriched in neural tissues in both vertebrates and invertebrates. However, the specific neurophysiological functions of most DEG/ENaC-encoding genes remain poorly understood. The fruit fly Drosophila melanogaster is an excellent model for deciphering the functions of DEG/ENaC genes because its genome encodes an exceptionally large number of DEG/ENaC subunits termed pickpocket (ppk) 1-31 Here we demonstrate that ppk29 contributes specifically to the postsynaptic modulation of excitatory synaptic transmission at the larval neuromuscular junction...
March 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28123080/cortactin-is-a-regulator-of-activity-dependent-synaptic-plasticity-controlled-by-wingless
#18
Daniel Alicea, Marizabeth Perez, Carolina Maldonado, Carihann Dominicci-Cotto, Bruno Marie
Major signaling molecules initially characterized as key early developmental regulators are also essential for the plasticity of the nervous system. Previously, the Wingless (Wg)/Wnt pathway was shown to underlie the structural and electrophysiological changes during activity-dependent synaptic plasticity at the Drosophila neuromuscular junction. A challenge remains to understand how this signal mediates the cellular changes underlying this plasticity. Here, we focus on the actin regulator Cortactin, a major organizer of protrusion, membrane mobility, and invasiveness, and define its new role in synaptic plasticity...
February 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28073926/mutations-of-pqbp1-in-renpenning-syndrome-promote-ubiquitin-mediated-degradation-of-fmrp-and-cause-synaptic-dysfunction
#19
Xiao-Yan Zhang, Junxia Qi, Yu-Qian Shen, Xian Liu, An Liu, Zikai Zhou, Junhai Han, Zi Chao Zhang
Renpenning syndrome is a group of X-linked intellectual disability syndromes caused by mutations in human polyglutamine-binding protein 1 (PQBP1) gene. Little is known about the molecular pathogenesis of the various mutations that cause the notable variability in patients. In this study, we examine the cellular and synaptic functions of the most common mutations found in the patients: c.461_462delAG, c.459_462delAGAG and c.463_464dupAG in an AG hexamer in PQBP1 exon 4. We discovered that PQBP1 c.459_462delAGAG and c...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/27916456/acute-fasting-regulates-retrograde-synaptic-enhancement-through-a-4e-bp-dependent-mechanism
#20
Grant Kauwe, Kazuya Tsurudome, Jay Penney, Megumi Mori, Lindsay Gray, Mario R Calderon, Fatima Elazouzzi, Nicole Chicoine, Nahum Sonenberg, A Pejmun Haghighi
While beneficial effects of fasting on organismal function and health are well appreciated, we know little about the molecular details of how fasting influences synaptic function and plasticity. Our genetic and electrophysiological experiments demonstrate that acute fasting blocks retrograde synaptic enhancement that is normally triggered as a result of reduction in postsynaptic receptor function at the Drosophila larval neuromuscular junction (NMJ). This negative regulation critically depends on transcriptional enhancement of eukaryotic initiation factor 4E binding protein (4E-BP) under the control of the transcription factor Forkhead box O (Foxo)...
December 21, 2016: Neuron
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