[PDF] Regulation And Transcriptional Role Of Crtc1 During Activity In Neurons eBook

Author : Martina DeSalvo
Publisher :
Page : 192 pages
File Size : 31,68 MB
Release : 2016
Category :
ISBN :

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Long term memory is mediated by long-lasting forms of synaptic plasticity that require new gene transcription for their persistence. Previous work has shown that neuronal CREB-regulated transcriptional coactivator 1 (CRTC1) plays a crucial role during learning and memory by regulating activity-dependent gene expression. We have shown that CRTC1 undergoes synapse-to-nucleus translocation to regulate transcription of CREB target genes in response to neuronal activity. In this thesis, we investigate the regulation and retrograde transport of CRTC1 in neurons and examine the nuclear role of CRTC1 in activity-dependent gene transcription. Our first goal was to identify the mechanisms by which CRTC1 responds to activity. We describe key synaptic processes necessary to trigger dephosphorylation of three serine residues that are required for dynein-mediated transport of CRTC1 to the nucleus. Our second goal was to understand the role of CRCT1 as a transcriptional coactivator. We use a combination of ChIP-seq, ATAC-seq and RNA-seq to understand how CRTC1 binding to CREB and other transcription factors correlates with changes in chromatin accessibility and transcription of activity-induced genes. Finally, we summarize a series of projects that attempt to elucidate how regulation of CRTC1's phosphorylation code may influence its function in neurons. These studies highlight the complexities of CRTC1 as an intrinsically disordered protein with 50 phosphorylated residues and a variety of potential interacting partners.

Author : Serena Dudek
Publisher : Springer Science & Business Media
Page : 426 pages
File Size : 32,33 MB
Release : 2007-11-24
Category : Medical
ISBN : 0387736093

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Regulation of gene transcription by neuronal activity is evident in a large number of neuronal processes ranging from neural development and refinement of neuronal connections to learning and response to injury. In the field of activity-dependent gene expression, rapid progress is being made that can impact these, and many other areas of neuroscience. This book offers an up-to-date picture of the field.

Author : Benedict C. Albensi
Publisher : Frontiers Media SA
Page : 118 pages
File Size : 28,39 MB
Release : 2016-09-06
Category : Neurosciences. Biological psychiatry. Neuropsychiatry
ISBN : 2889198650

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The formation of various forms of memory involves a series of distinct cellular and molecular mechanisms, many of which are not fully understood. There are highly conserved pathways that are involved in learning, memory, and synaptic plasticity, which is the primary substrate for memory storage. The formation of short-term (across minutes) memory is mediated by local changes in synapses, while long-term (across hours to days) memory storage is associated with activation of transcription and synthesis of proteins that modify synaptic function. Transcription factors, which can either repress or activate transcription, play a vital role in driving protein synthesis underlying synaptic plasticity and memory, whereby protein synthesis provides the necessary building blocks to accommodate structural changes at the synapse that foster memory formation. Recent data implicate several families of transcription factors that appear critically important in the regulation of memory. In this Topic we will focus on the families of transcription factors thus far found to be critically involved in synaptic plasticity and memory formation. These include cAMP response element binding protein (CREB), Rel/nuclear factor B (Rel/NFB), CCAAT enhancer binding protein (C/EBP), and early growth response factor (Egr). In recent years, numerous studies have implicated epigenetic mechanisms, changes in gene activity and expression that occur without alteration in gene sequence, in the memory consolidation process. DNA methylation and chromatin remodeling are critically involved in learning and memory, supporting a role of epigenetic mechanisms. Here we provide more evidence of the importance of DNA methylation, histone posttranslational modifications and the role of histone acetylation and HDAC inhibitors in above mentioned processes.

Author : Shivan Luca Bonanno
Publisher :
Page : 208 pages
File Size : 29,11 MB
Release : 2018
Category :
ISBN :

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Synaptic plasticity, the change in number, position, and strength of synapses, requires the synthesis of new cellular components that contribute to changes in synaptic composition, and it has long-been appreciated that there is an important role for de novo transcription in the maintenance of long-term potentiation (LTP). As plasticity-inducing signals are received at synapses that can be hundreds of microns away from the cell's nucleus, which contains its transcriptional machinery, a signal must be faithfully communicated from synapse to nucleus. CREB-Regulated Transcription Coactivator 1 (CRTC1) acts as a retrograde signaling molecule that travels from stimulated synapses to the nucleus, where it alters gene expression through interactions with bZIP transcription factors such as CREB. CRTC1 has been shown to be necessary for the maintenance of long-term potentiation in the hippocampus, and undergoes dramatic and complex post-translational modifications that correlate with its nuclear transport following synaptic activity. There is little known, however, about the transcriptional targets of CRTC1 after plasticity-induction, and whether it may play a role in modulating specific programs of gene expression during different types of long-term plasticity. To address this question, I first investigated the nuclear translocation of CRTC1 in response to different plasticity-induction protocols. Next, I optimized a Chromatin Immunoprecipitation-sequencing (ChIP-seq) protocol to investigate the genomic targets of CRTC1 following dihydroxyphenylglycine (DHPG)-induced long-term depression (LTD) in CA1 cells of the hippocampus, and found that CRTC1-containing protein complexes occupy loci including transcriptional start sites, promoters, enhancers, gene bodies, and intergenic regions. The genes associated with these loci include, but are not limited to, immediate-early genes, as well as other important neuronal genes. Finally, I conducted ChIP-seq and RNA-seq on a wider set of stimulations, including an LTP and a different LTD protocol in addition to control and DHPG-LTD samples. Data analysis for this work is ongoing and will allow correlation of transcript level with the genomic targets of CRTC1. Through this work emerges a clearer view of the genomic targets of CRTC1 during the induction of bidirectional synaptic plasticity in the hippocampus, as well as a modified protocol for conducting ChIP-seq from rodent adult brain tissue.

Author : Ramendra N. Saha
Publisher : Springer
Page : 0 pages
File Size : 43,96 MB
Release : 2024-11-01
Category : Science
ISBN : 9783031685491

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This book discusses the regulation of gene transcription by neuronal activity that is evident in a large number of neuronal processes ranging from neural development and refinement of neuronal connections to learning and response to injury. Transcriptional Regulation by Neuronal Activity: To the Nucleus and Back, 2nd edition illustrates how signals are transmitted to the nucleus in response to neuronal activity, which genes are regulated and how this is achieved, and how these changes in gene expression alter neuronal function. The aim of this second edition is to highlight key advances in the field since the first edition. The book is divided into four sections. The first highlights how signals get to the nucleus from the membrane in response to synaptic or neuronal activity. Included are chapters on the pathways that transmit signals from synapses to nuclei. The second section focuses on epigenetic regulatory processes of activity-induced gene transcription, an area that has exploded in the past few years. The third section navigates the role of activity-induced genes in physiological processes such as learning and memory, and human developmental disorders such as those associated with the autism spectrum. The fourth section highlights groundbreaking technological advances in the field, which have allowed activity-regulated transcription to be used as a tool to study learning and memory.

Author : Anna Maria Giuffrida Stella
Publisher :
Page : 504 pages
File Size : 31,45 MB
Release : 1990-07-19
Category : Medical
ISBN :

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Offers an up-to-date account of the latest research findings concerned with the regulatory mechanisms of gene expression in neuronal and glial cells under different conditions. The book explores the cellular and neurobiological aspects of important phenomena of the nervous system and its role in health, disease and injury. Contributions from prominent scientists in the field address a variety of specific topics concerned with gene expression in the nervous system--from growth, hormonal and trophic factors to neural tissue reactions in injury or aging.

Author :
Publisher : Academic Press
Page : 378 pages
File Size : 23,8 MB
Release : 2019-05-24
Category : Medical
ISBN : 0128137975

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Chromatin Signaling and Neurological Disorders, Volume Seven, explores our current understanding of how chromatin signaling regulates access to genetic information, and how their aberrant regulation can contribute to neurological disorders. Researchers, students and clinicians will not only gain a strong grounding on the relationship between chromatin signaling and neurological disorders, but they'll also discover approaches to better interpret and employ new diagnostic studies and epigenetic-based therapies. A diverse range of chapters from international experts speaks to the basis of chromatin and epigenetic signaling pathways and specific chromatin signaling factors that regulate a range of diseases. In addition to the basic science of chromatin signaling factors, each disease-specific chapter speaks to the translational or clinical significance of recent findings, along with important implications for the development of epigenetics-based therapeutics. Common themes of translational significance are also identified across disease types, as well as the future potential of chromatin signaling research. Examines specific chromatin signaling factors that regulate spinal muscular atrophy, ulbospinal muscular atrophy, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, multiple sclerosis, Angelman syndrome, Rader-Willi syndrome, and more Contains chapter contributions from international experts who speak to the clinical significance of recent findings and the implications for the development of epigenetics-based therapeutics Provides researchers, students and clinicians with approaches to better interpret and employ new diagnostic studies for treating neurological disorders

Author : Estela Maris Muñoz
Publisher : Frontiers Media SA
Page : 169 pages
File Size : 28,20 MB
Release : 2023-10-03
Category : Science
ISBN : 2832533817

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A finely tuned regulation of gene expression is essential for shaping the nervous system and for maintaining its homeostasis throughout life. Disruptions in gene regulation can impact brain development and physiology in ways that contribute to diverse pathologies. The master orchestrators of gene activity in the nucleus are transcription factors, proteins that recognize and bind to specific DNA motifs in regulatory regions and drive changes in gene expression. Transcription factors act with the help of other co-factor proteins, including components of the Mediator complex, histone modifying enzymes, chromatin modelers, and DNA methylases. In addition, transcription factor activity in the nervous system can be modulated by extracellular signals, including growth factors, hormones, neuropeptides and neurotransmitters that activate specific receptors and intracellular transduction pathways. An in-depth understanding of the mechanisms of transcription regulation is needed in order to better describe how each element, from genes to cells, defines and maintains identities and functionalities in the healthy and diseased brain. This Research Topic is oriented to developing an integrative view about transcription regulation within the nervous system, focusing on developmental and homeostatic processes, dysregulation in functionality and expression levels and consequent associated pathologies such as neurodevelopmental disorders, brain tumors, and neurodegenerative diseases. Transcription regulation investigations will specifically focus on transcription factors that belong to the bHLH (e.g. NeuroD), homeobox (e.g. Islet, Pax, Rax, and Lhx) and CREB families, and on their roles over defined nervous system areas: cerebral cortex, thalamic and hypothalamic areas, interacting with the developing brain.

Author : Tamara Luti Rosenbaum Emir
Publisher : CRC Press
Page : 327 pages
File Size : 48,24 MB
Release : 2017-08-09
Category : Science
ISBN : 1498755267

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During the last two decades, there has been an explosion of research pertaining to the molecular mechanisms that allow for organisms to detect different stimuli that is an essential feature for their survival. Among these mechanisms, living beings need to be able to respond to different temperatures as well as chemical and physical stimuli. Thermally activated ion channels were proposed to be present in sensory neurons in the 1980s, but it was not until 1997 that a heat- and capsaicin- activated ion channel, TRPV1, was cloned and its function described in detail. This groundbreaking discovery led to the identification and characterization of several more proteins of the family of Transient Receptor Potential (TRP) ion channels. Intensive research has provided us with the atomic structures of some of these proteins, as well as understanding of their physiological roles, both in normal and pathological conditions. With chapters contributed by renowned experts in the field, Neurobiology of TRP Channels contains a state- of- the- art overview of our knowledge of TRP channels, ranging from structure to their functions in organismal physiology. Features: • Contains chapters on the roles of several TRP ion channels with a diversity of physiological functions, providing a complete picture of the widespread importance of these proteins. • Presents an overview of the structure of TRP channels, including the roles of these proteins in different physiological processes. • Discusses the roles of TRP channels in pathophysiological processes, further highlighting their importance. • Features several full color illustrations to allow the reader better comprehension of TRP channels. A volume in the Frontiers in Neuroscience series

Author :
Publisher : ScholarlyEditions
Page : 3143 pages
File Size : 35,96 MB
Release : 2012-01-09
Category : Medical
ISBN : 1464963614

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Issues in Neuroscience Research and Application: 2011 Edition is a ScholarlyEditions™ eBook that delivers timely, authoritative, and comprehensive information about Neuroscience Research and Application. The editors have built Issues in Neuroscience Research and Application: 2011 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Neuroscience Research and Application in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Issues in Neuroscience Research and Application: 2011 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.