Molecular and Genetic Analysis of Synaptic Signaling in Drosophila PDF Download
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Author:
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Languages : en
Pages : 278
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Book Description
Molecular and genetic analysis of synaptic signaling in Drosophila has yielded many insights into nervous system development, properties of synaptic transmission, and how long-lasting changes in neurons occur. Synaptic signaling components required for synaptic transmission and pathways leading to nervous system plasticity are typically conserved from insects to humans. The role of proteins and genes in synaptic function in flies can be analyzed from the level of a single synapse to complex behaviors in the whole organism. Because of a fully sequenced genome and the ease of mutagenesis in flies, genetic screens have been useful in identifying novel regulators of synaptic transmission and long-term memory. In flies, conditional mutations affecting synaptic transmission at nerve terminals often lead to temperature sensitive paralysis. In a screen for mutations that interact with Drosophila shibirets mutants, the stoned gene was identified as a regulator of synaptic vesicle cycling. Stoned encodes two neuronally expressed proteins, stonedA and B, which are required for synaptic vesicle recycling and normal synaptic transmission. However, the exact functions of the two stoned proteins are not fully understood. We investigate distinct roles of the stoned proteins here and show that stoned has a novel role in synaptic growth. Memory in flies can be divided into genetically distinct phases based on the requirement for protein synthesis and activation of the transcription factor CREB. Novel regulators of long-term olfactory avoidance memory were isolated in a mutant screen in flies. Mutants in the Drosophila gene lk6, homologous to the translational regulator MNK, have defects in long-term olfactory avoidance memory. We find that lk6 is highly expressed in the fly nervous system, and is activated by and functions downstream of Ras/ERK signaling in fly neurons. Insights provided here from Drosophila add to the evidence that MNK may be the link between ERK signaling and the regulation of translation in long-term plasticity. Ultimately, understanding synaptic function has therapeutic potential to aid in alleviation of nervous system dysfunction. Insight into the molecular pathways underlying plasticity and long-term memory gained from studies in flies, mollusks, and rodents has been pivotal in the development of potential drugs to aid in memory deficits in humans.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 278
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Book Description
Molecular and genetic analysis of synaptic signaling in Drosophila has yielded many insights into nervous system development, properties of synaptic transmission, and how long-lasting changes in neurons occur. Synaptic signaling components required for synaptic transmission and pathways leading to nervous system plasticity are typically conserved from insects to humans. The role of proteins and genes in synaptic function in flies can be analyzed from the level of a single synapse to complex behaviors in the whole organism. Because of a fully sequenced genome and the ease of mutagenesis in flies, genetic screens have been useful in identifying novel regulators of synaptic transmission and long-term memory. In flies, conditional mutations affecting synaptic transmission at nerve terminals often lead to temperature sensitive paralysis. In a screen for mutations that interact with Drosophila shibirets mutants, the stoned gene was identified as a regulator of synaptic vesicle cycling. Stoned encodes two neuronally expressed proteins, stonedA and B, which are required for synaptic vesicle recycling and normal synaptic transmission. However, the exact functions of the two stoned proteins are not fully understood. We investigate distinct roles of the stoned proteins here and show that stoned has a novel role in synaptic growth. Memory in flies can be divided into genetically distinct phases based on the requirement for protein synthesis and activation of the transcription factor CREB. Novel regulators of long-term olfactory avoidance memory were isolated in a mutant screen in flies. Mutants in the Drosophila gene lk6, homologous to the translational regulator MNK, have defects in long-term olfactory avoidance memory. We find that lk6 is highly expressed in the fly nervous system, and is activated by and functions downstream of Ras/ERK signaling in fly neurons. Insights provided here from Drosophila add to the evidence that MNK may be the link between ERK signaling and the regulation of translation in long-term plasticity. Ultimately, understanding synaptic function has therapeutic potential to aid in alleviation of nervous system dysfunction. Insight into the molecular pathways underlying plasticity and long-term memory gained from studies in flies, mollusks, and rodents has been pivotal in the development of potential drugs to aid in memory deficits in humans.
Author: Hong Iris Wan
Publisher:
ISBN:
Category :
Languages : en
Pages : 392
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Author: Janani Iyer
Publisher:
ISBN:
Category :
Languages : en
Pages : 198
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Author: Sophie Ann Petersen
Publisher:
ISBN:
Category :
Languages : en
Pages : 252
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Author: Huidy Shu
Publisher:
ISBN:
Category :
Languages : en
Pages : 336
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Book Description
Author: C.S. Lu
Publisher: Elsevier Inc. Chapters
ISBN: 0128062827
Category : Medical
Languages : en
Pages : 98
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Author: Wolfgang B. Liedtke, MD, PH.D.
Publisher: CRC Press
ISBN: 1420005847
Category : Medical
Languages : en
Pages : 502
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Book Description
Since the first TRP ion channel was discovered in Drosophila melanogaster in 1989, the progress made in this area of signaling research has yielded findings that offer the potential to dramatically impact human health and wellness. Involved in gateway activity for all five of our senses, TRP channels have been shown to respond to a wide range of st
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Category :
Languages : en
Pages : 129
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Book Description
Synapses are the basic units of neural structure and function. Proper synaptic growth is essential for normal development of the nervous system and its function in mediating complex behaviors such as learning and memory. In my dissertation work, I took a combined approach of genetics, molecular biology and biochemistry to identify genes and molecular pathways that regulate synaptic growth in Drosophila, and discovered neuropeptide signaling as a novel mechanism in this process. Neuropeptides have been known to affect neuronal excitability and the strength of synaptic transmission. However, neuropeptides have not been clearly implicated in synaptic growth and development. Through forward genetics, I discovered a cholecystokinin-like receptor (CCKLR) and its predicted ligand drosulfakinin (DSK), as components of a signaling pathway that strongly promote growth of the Drosophila larval neuromuscular junction (NMJ). Loss-of-function mutations of CCKLR or dsk produce severe NMJ undergrowth, whereas over-expression of CCKLR leads to NMJ overgrowth. Through targeted RNAi expression and transgenic rescue experiments I show that presynaptic expression of CCKLR in motor neurons is necessary and sufficient for regulation of NMJ growth. Through analysis of double mutants, I have dissected the signaling pathway downstream of the receptor. I show that this pathway involves G-protein-dependent stimulation of adenyl cyclase to activate PKA, which in turn activates CREB, the cAMP-response element binding protein. In addition, I demonstrate that DSK activates CCKLR biochemically, and that DSK/CCKLR signaling affects synaptic transmission and larval locomotor behavior. To discover novel genes that interact with the CCKLR-signaling pathway to regulate NMJ growth, I performed a modifier screen using chromosomal deficiencies. This pilot screen has identified several regions on the second and third chromosomes that dominantly enhance or suppress the NMJ phenotype of CCKLR mutants. Intriguingly, a number of neuropeptide signaling molecules were found among the candidate interacting genes. Specifically, I have found that leucokinin (DLK) and leucokinin receptor (LKR) negatively regulate NMJ growth, and strongly interact with CCKLR. The results of the modifier screen suggest that neuropeptide signaling may be a more common mechanism for regulating NMJ growth than previously realized and many of the molecules are yet to be uncovered.
Author: Xiaomin Xing
Publisher:
ISBN:
Category : Calcium
Languages : en
Pages : 132
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Book Description
Ca2+ influx is one of the critical events that trigger synaptic vesicular release, and the accumulation of residual free Ca2+ in synapses is also important for activity-dependent synaptic plasticity. Ca2+ imaging with fluorescence indicators (synthetic or genetically encoded) is a powerful approach to monitor Ca2+ levels in neurons and synapses. Although accumulating studies in vertebrate systems have been carried out to demonstrate the role of Ca2+ in synaptic transmission and plasticity, most of these studies rely on pharmacological methods to infer the molecular mechanism, with less emphasis on forward genetic analysis. The Drosophila neuromuscular junction (NMJ) is a powerful neurogenetic platform for studying synaptic transmission, because of the availability of many mutations. However, not many mutations have been analyzed with Ca2+ imaging. Besides, although Genetically Encoded Ca2+ Indicators (GECIs) including GCaMPs are increasingly popular as the tool to identify neuronal circuits activated by certain stimuli or mediating particular behaviors, the physiological and functional interpretation of neuronal Ca2+ transients reported by GECIs remain obscure. By expressing GCaMPs in NMJ synapses, I characterized a spectrum of genetic mutations including sodium channel alleles parats1, parabss1, potassium channel mutations Shaker (ShM, Sh120), Shab3, ether-a-go-go (eag1, eag4pm), and double mutant eag1 Sh120. Drosophila NMJs contain at least three different types of synapses, which include glutamatergic tonic motor synapse type Ib, phasic motor synapse type Is, and modulatory octopaminergic synapse type II. In this study, I found that the ion channel mutations did not uniformly alter the Ca2+ dynamics in type Ib, Is and II synapses.
Author:
Publisher: Academic Press
ISBN: 0080857779
Category : Science
Languages : en
Pages : 317
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Book Description
Neuromuscular Junctions in Drosophila gathers the main contributions that research using the fruit fly Drosophila melanogaster has made in the area of synapse development, synapse physiology, and excitability of muscles and nerve cells. The chapters in this book represent a synthesis of major advances in our understanding of neuronal development and synaptic physiology, which have been obtained using the above approach.This book is directed to the general neuroscience audience: researchers, instructors, graduate students, and advanced undergraduates who are interested in the mechanisms of synapse development and physiology. However, the book will also be a valuable resource for those that use the fruit fly as a model system in their laboratories. Key Features* Synthesizes the genetic approaches used to study synaptic development and function at the neuromuscular junction, using flies as a model system* Covers major recent advances in muscle development, pathfinding, synapse maturation and plasticity, exo- and endocytosis, and ion channel function* Written in clear language that is easily understandable to readers not already familiar with fruit fly research* Includes numerous diagrams and extensive reference lists
