The Characterization of the Signaling Adapter Protein Fibroblast Growth Factor Receptor Substrate 3 and Its Role in Regulating Microtubule Dynamics and Molecular Transport in the Brain PDF Download
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Author: Sarah Justina Gamble
Publisher:
ISBN:
Category :
Languages : en
Pages : 230
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Book Description
The neuronal cytoskeleton is responsible for governing dynamics such as neurite extension and cortex development. In particular, microtubules (MTs) and their associated proteins, and molecular motors, have been shown to be critical in many neuronal processes such as intracellular molecular transport and neuron differentiation. The fibroblast growth factors (FGFs) act as powerful morphogens that have been shown to play a role in regulating cortical development. FGFs activate receptor tyrosine kinases, of which fibroblast growth factor receptor substrate 3 (FRS3) has been shown to interact with, to mediate downstream signaling cascades (regulating cell proliferation and differentiation). In addition to FRS3 and its role in signaling, preliminary evidence suggested that FRS3 is a novel MT binding protein, and also interacts with MT associated proteins and the molecular motor kinesin. Furthermore, the expression of FRS3 has been shown to coincide with migrating cortical neurons from E12 cortical precursor cell cultures. This thesis hypothesized that FRS3 regulates the differentiation and maturation of neurons as well as post-mitotic neuron function by regulating MT stability and intracellular transport of cargo and organelles. The research presented here has addressed this hypothesis in a multidisciplinary manner. First, FRS3 and its MT binding properties and its interactions with various proteins involved in molecular transport within cortical and hippocampal neurons (including motors, adapters and cargo) were investigated. FRS3 was shown to interact with markers of migrating and post-mitotic neurons (acetylated alpha and Beta III tubulin, respectively), postsynaptic density scaffolding proteins (Shank 2 and 3), cargo (Flg/FGFR1), molecular motor components (Kinesin Heavy Chain and Kinesin Light Chain), synaptic vesicle proteins (Syntaxin I and Synaptophysin) and finally MT associated proteins (MAP2, Doublecortin and Tau). Next, loss of FRS3 expression in SN56 cells resulted in increased sensitivity to the MT depolymerizing agent nocodazole, suggesting FRS3 is necessary for proper MT dynamics. Furthermore, loss of FRS3, but not the related signaling adaptor FRS2, resulted in impaired neurite outgrowth in both hippocampal and cortical cell culture. These results, taken together, suggest that FRS3, in addition to its role in FGF signaling, also interacts with members of the molecular transport machinery and confers stability to microtubules.
Author: Sarah Justina Gamble
Publisher:
ISBN:
Category :
Languages : en
Pages : 230
Get Book Here
Book Description
The neuronal cytoskeleton is responsible for governing dynamics such as neurite extension and cortex development. In particular, microtubules (MTs) and their associated proteins, and molecular motors, have been shown to be critical in many neuronal processes such as intracellular molecular transport and neuron differentiation. The fibroblast growth factors (FGFs) act as powerful morphogens that have been shown to play a role in regulating cortical development. FGFs activate receptor tyrosine kinases, of which fibroblast growth factor receptor substrate 3 (FRS3) has been shown to interact with, to mediate downstream signaling cascades (regulating cell proliferation and differentiation). In addition to FRS3 and its role in signaling, preliminary evidence suggested that FRS3 is a novel MT binding protein, and also interacts with MT associated proteins and the molecular motor kinesin. Furthermore, the expression of FRS3 has been shown to coincide with migrating cortical neurons from E12 cortical precursor cell cultures. This thesis hypothesized that FRS3 regulates the differentiation and maturation of neurons as well as post-mitotic neuron function by regulating MT stability and intracellular transport of cargo and organelles. The research presented here has addressed this hypothesis in a multidisciplinary manner. First, FRS3 and its MT binding properties and its interactions with various proteins involved in molecular transport within cortical and hippocampal neurons (including motors, adapters and cargo) were investigated. FRS3 was shown to interact with markers of migrating and post-mitotic neurons (acetylated alpha and Beta III tubulin, respectively), postsynaptic density scaffolding proteins (Shank 2 and 3), cargo (Flg/FGFR1), molecular motor components (Kinesin Heavy Chain and Kinesin Light Chain), synaptic vesicle proteins (Syntaxin I and Synaptophysin) and finally MT associated proteins (MAP2, Doublecortin and Tau). Next, loss of FRS3 expression in SN56 cells resulted in increased sensitivity to the MT depolymerizing agent nocodazole, suggesting FRS3 is necessary for proper MT dynamics. Furthermore, loss of FRS3, but not the related signaling adaptor FRS2, resulted in impaired neurite outgrowth in both hippocampal and cortical cell culture. These results, taken together, suggest that FRS3, in addition to its role in FGF signaling, also interacts with members of the molecular transport machinery and confers stability to microtubules.
Author:
Publisher: Academic Press
ISBN: 0080962823
Category : Science
Languages : en
Pages : 423
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Book Description
In recent years, the role of cilia in the study of health, development and disease has been increasingly clear, and new discoveries have made this an exciting and important field of research. This comprehensive volume, a complement to the new three-volume treatment of cilia and flagella by King and Pazour, presents easy-to-follow protocols and detailed background information for researchers working with cilia and flagella. Covers protocols for primary cilia across several systems and species Both classic and state-of-the-art methods readily adaptable across model systems, and designed to last the test of time Relevant to clinicians and scientists working in a wide range of fields
Author: Kermit L. Carraway
Publisher: Springer Science & Business Media
ISBN: 3662129930
Category : Science
Languages : en
Pages : 293
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Book Description
This monograph explores the relationships between cell signaling and the cytoplasmic cytoskeleton in fundamental cell processes, thus bridging the gap between two very active aspects of molecular cell biology. It covers the two main - and reciprocal - questions of these relationships: How are structure and function of the cytoskeleton affected by external signals which impinge on the cell? How does the cytoskeleton influence the cellular signaling processes which determine cell behavior?
Author: Hirokawa
Publisher: CRC Press
ISBN: 9780849377419
Category : Science
Languages : en
Pages : 360
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Book Description
This book discusses the primary functions of microtubule-associated proteins (MAPs) such as MAP2 and tau in neuronal morphogenesis, as well as relationships between neuronal differentiation and the expression of neuronal intermediate filaments (nestin, alpha internexin, and neurofilament triplet proteins). It emphasizes the importance of several cytoskeletal proteins for neuronal differentiation and morphogenesis, organelle transport, and synaptic functions. The book considers the involvement of tau MAPs in the formation of paired helical filaments in Alzheimer's disease, and it examines the mechanisms of organelle transports and molecular motors such as kinesin, braindynein, and kinesin superfamily proteins. Cytoskeletal proteins involved in synaptic formation and transmitter release and new synaptic junctional-associated proteins are explored as well.
Author: Francesc Posas
Publisher: Springer Science & Business Media
ISBN: 3540755691
Category : Science
Languages : en
Pages : 322
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Book Description
In this book leading researchers in the field discuss the state-of-the-art of many aspects of SAPK signaling in various systems from yeast to mammals. These include various chapters on regulatory mechanisms as well as the contribution of the SAPK signaling pathways to processes such as gene expression, metabolism, cell cycle regulation, immune responses and tumorigenesis. Written by international experts, the book will appeal to cell biologists and biochemists.
Author: Neurosciences Institute (New York, N.Y.)
Publisher: Wiley-Interscience
ISBN:
Category : Medical
Languages : en
Pages : 808
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Book Description
This book consists of five sections. The first section details methods for analyzing both presynaptic and postsynaptic function and emphasizes the molecular aspects of synapses. It describes ongoing studies of neurotransmitter release, voltage- sensitive ion channels, and electronic transmission at gap junctions. The second section focuses on the growing menagerie of neurotransmitters: their catagorization into chemical families, their relation to ion channels, their modulation by second messenger systems and their role in pharmacologic action. The third section considers the important relationship of transmitter diversity and synaptic types to the behavior of actual cellular networks. All of the studies described in these sections point to the necessity of considering interactions between anatomy, chemistry, physiology and pharmacology if synaptic function is to be understood at any one of these levels of analysis.
Author: Cai Huang
Publisher: BoD – Books on Demand
ISBN: 9535107372
Category : Medical
Languages : en
Pages : 482
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Book Description
15 chapters on protein phosphorylation and human health written by expert scientists. Covers most important research hot points, such as Akt, AMPK and mTOR. Bridges the basic protein phosphorylation pathways with human health and diseases. Detailed and comprehensive text with excellent figure illustration.
Author: Marie-France Carlier
Publisher: Springer Science & Business Media
ISBN: 904819301X
Category : Medical
Languages : en
Pages : 434
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Book Description
Since the discovery of actin by Straub in the 1950’s and the pioneering work of Oosawa on actin self-assembly in helical laments in the 1960’s, many books and conference proceedings have been published. As one of the most essential p- teins in life, essential for movement in organisms rangingfrom bacteria to higher eukaryotes, it is no surprise that actin has fascinated generations of scientists from many different elds. Actin can be considered as a “living treasure” of biology; the kinetics and thermodynamics of self-assembly, the dissipative nature of actin po- merization, the molecular interactions of monomeric and polymerized actin with regulators, the mechanical properties of actin gels, and more recently the force p- ducing motile and morphogenetic processes organized by the actin nanomachine in response to signaling, are all milestones in actin research. Discoveries that directly derive from and provide deeper insight into the fundamental properties of actin are constantly being made, making actin an ever appealing research molecule. At the same time, the explosion in new technologies and techniques in biological sciences has served to attract researchers from an expanding number of disciplines, to study actin. This book presents the latest developments of these new multiscale approaches of force and movement powered by self-assembly processes, with the hope to opening our perspectives on the many areas of actin-based motility research.
Author: Anne Straube
Publisher: Humana Press
ISBN: 9781493961856
Category : Science
Languages : en
Pages : 319
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Book Description
Microtubules are at the heart of cellular self-organization, and their dynamic nature allows them to explore the intracellular space and mediate the transport of cargoes from the nucleus to the outer edges of the cell and back. In Microtubule Dynamics: Methods and Protocols, experts in the field provide an up-to-date collection of methods and approaches that are used to investigate microtubule dynamics in vitro and in cells. Beginning with the question of how to analyze microtubule dynamics, the volume continues with detailed descriptions of how to isolate tubulin from different sources and with different posttranslational modifications, methods used to study microtubule dynamics and microtubule interactions in vitro, techniques to investigate the ultrastructure of microtubules and associated proteins, assays to study microtubule nucleation, turnover, and force production in cells, as well as approaches to isolate novel microtubule-associated proteins and their interacting proteins. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Definitive and practical, Microtubule Dynamics: Methods and Protocols provides the key protocols needed by novices and experts on how to perform a broad range of well-established and newly-emerging techniques in this vital field.
Author: Vladimir Parpura
Publisher: Springer Science & Business Media
ISBN: 0387794921
Category : Medical
Languages : en
Pages : 701
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Book Description
Astrocytes were the original neuroglia that Ramón y Cajal visualized in 1913 using a gold sublimate stain. This stain targeted intermediate filaments that we now know consist mainly of glial fibrillary acidic protein, a protein used today as an astrocytic marker. Cajal described the morphological diversity of these cells with some ast- cytes surrounding neurons, while the others are intimately associated with vasculature. We start the book by discussing the heterogeneity of astrocytes using contemporary tools and by calling into question the assumption by classical neuroscience that neurons and glia are derived from distinct pools of progenitor cells. Astrocytes have long been neglected as active participants in intercellular communication and information processing in the central nervous system, in part due to their lack of electrical excitability. The follow up chapters review the “nuts and bolts” of ast- cytic physiology; astrocytes possess a diverse assortment of ion channels, neu- transmitter receptors, and transport mechanisms that enable the astrocytes to respond to many of the same signals that act on neurons. Since astrocytes can detect chemical transmitters that are released from neurons and can release their own extracellular signals there is an increasing awareness that they play physiological roles in regulating neuronal activity and synaptic transmission. In addition to these physiological roles, it is becoming increasingly recognized that astrocytes play critical roles during pathophysiological states of the nervous system; these states include gliomas, Alexander disease, and epilepsy to mention a few.
