Drebrin
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Drebrin
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Author : Tomoaki Shirao
language : en
Publisher: Springer
Release Date : 2017-08-31
Drebrin written by Tomoaki Shirao and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-08-31 with Medical categories.
This book is the first comprehensive review of drebrin, which plays pivotal roles in various cellular events, via forming unique actin cytoskeletons, including synapse formation and in synaptic function. Particularly the loss of drebrin from dendritic spines is used as a marker of dementia in neurological disorders such as Alzheimer’s disease. Since drebrin was first identified by our group in 1985, many studies of drebrin have been done in various fields, including not only molecular biology, biophysics, cell biology, neuroscience, clinical studies, spermatogenesis, immunology, and cancer metastasis, but others as well. The structure of this book facilitates the understanding of the whole picture of studies on drebrin. The volume begins with a general introduction to drebrin, and then the chapters in the second part provide the basic knowledge for further understanding. The third part examines its function in the nervous system, and the fourth part discusses its function in the non-nervous system. This work will appeal to researchers who are interested in cytoskeletal dynamics at membrane-cytoskeletal interface as well as the number of them who use drebrin as a tool, such as a marker of synaptic function or a disease marker. This volume is kept as concise as possible in order to be understood by readers in diverse scientific disciplines.
Regulation Of Drebrin In Dendritic Spines By Egr 1 Transcription Factor
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Author : Chulmin Cho
language : en
Publisher:
Release Date : 2016
Regulation Of Drebrin In Dendritic Spines By Egr 1 Transcription Factor written by Chulmin Cho and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with categories.
"Dendritic spines are the actin-enriched protrusions on dendritic shafts that encase the postsynaptic machinery. The basis for morphological plasticity of dendritic spines is formed by changes in the actin cytoskeleton, which in turn, is orchestrated by actin binding proteins. A dynamic actin cytoskeleton allows the dendritic spines to rapidly and accordingly respond to various stimuli by changing their morphology, and this morphological plasticity ultimately leads to synaptic plasticity. In neurodegenerative diseases such as Alzheimer's disease (AD), this dynamicity inside dendritic spines is disrupted. Consequently, the dendritic spines are lost, which causes the loss of synapses. These findings highlight the importance of understanding the regulators of actin dynamics and the mechanisms leading to loss of dendritic spines. Drebrin is a F-actin binding protein that localizes to dendritic spines in the brain. Drebrin is required for synapse formation and structural plasticity during development as well as the process of learning and memory formation. Precipitous loss of drebrin has been observed in AD and other neurodegenerative diseases with synaptic pathology. However, the regulatory factor causing loss of drebrin in AD-related synaptic pathology remains elusive. Early growth response-1 (Egr-1) is an inducible zinc-finger transcription factor expressed in the brain that binds to the GC-rich consensus sequences on target promoters to regulate expression. Upregulation of Egr-1 has been found in AD brain. Herein, we hypothesized that Egr-1 downregulates drebrin expression and leads to synaptic dysfunction. We demonstrate that Egr-1 transcription factor binds to drebrin promoter. In silico analysis was performed to identify putative Egr-1 response elements (EREs) on drebrin promoter. To substantiate this, luciferase promoter assay and chromatin immunoprecipitation assay was used and confirmed Egr-1 binding to drebrin promoter both in vitro and in vivo. Further, we demonstrate that Egr-1 negatively regulates drebrin mRNA and protein level. In primary hippocampal neurons and an inducible mouse model of Egr-1 overexpression, drebrin was downregulated upon Egr-1 upregulation. Conversely, an increase in drebrin mRNA and protein level was observed in Egr-1 -/- mouse. Furthermore, it was shown that Egr-1-mediated loss of drebrin parallels decrease in dendritic spine density. Immunocytochemical analysis revealed reduction in the density of dendritic protrusions upon Egr-1 upregulation. Reduction in spine density was observed in the CA1 region of the hippocampus in Egr-1 Tg mouse while an increase was observed in samples from Egr-1 -/- mouse. Immunocytochemical colocalization study also showed concurrent loss of vGLUT1 and PSD-95, suggesting a loss of putative functional synapses. We also demonstrate that Egr-1 upregulation mediates changes in other synaptic proteins in primary hippocampal neurons. In summary our data show that 1) Egr-1 downregulates drebrin by binding to drebrin promoter, 2) Egr-1 is inversely correlated with dendritic spine density and 3) Egr-1 mediates decrease in postsynaptic proteins and putative synaptic contacts. Therefore, we conclude that Egr-1 is a key regulator of drebrin and consequently, chronic upregulation of Egr-1 may exacerbate synaptic pathology in AD and AD-related disorders." --
Turnover And Localization Of The Actin Binding Protein Drebrin In Neurons
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Author : Eugenia Rojas Puente
language : en
Publisher:
Release Date : 2016
Turnover And Localization Of The Actin Binding Protein Drebrin In Neurons written by Eugenia Rojas Puente and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with categories.
Molecular Mechanisms Controlling Drebrin Regulation And Its Function At The Dendritic Spines
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Author : Rita Björg Hendricusdóttir
language : en
Publisher:
Release Date : 2012
Molecular Mechanisms Controlling Drebrin Regulation And Its Function At The Dendritic Spines written by Rita Björg Hendricusdóttir and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with Actin categories.
Filamentous actin represents the major cytoskeletal component in dendritic spines and filopodia. Changes in spine and filopodia shape, size and number are determined by local actin remodelling. The actin-binding protein drebrin, which localises to dendritic spine and filopodia can regulate changes in spine and filopodia morphology. Overexpression of drebrin in hippocampal neurons induces the appearance of abnormally long dendritic spines, whilst loss of drebrin inhibits the overall number of synapses in hippocampal neurons. The precise mechanism of drebrin regulation or the exact function of drebrin in mediating spine and filopodia morphological changes is not completely understood. -- Drebrin is a phospho-protein and 17 phosphorylation sites have been identified by mass spectrometry. To investigate how phosphorylation of drebrin is regulated we raised phospho-specific antibodies, which were tested in cortical neurons treated with a panel of kinase inhibitors. The results show that different signalling pathways regulate drebrin phosphorylation at different phosphorylation sites. S142-drebrin phosphorylation is regulated upon synaptic activation while lithium, which is widely used to treat bipolar disease, is one of the kinase inhibitor that is involved in regulation of T392-drebrin phosphorylation. -- I also studied the function of drebrin regulation in filopodia morphology and dynamics. To analyse the motility of filopodia, a semi-automated Matlab program was developed. The results show that dendritic filopodia motility are increased in drebrin overexpressing neurons and this dynamics is regulated by pT392-drebrin. -- This study demonstrates that phosphorylation of drebrin can be regulated and the function of this regulation is involved in dynamic property of filopodia. In addition, the results suggest a novel lithium sensitive signalling pathway in the regulation of drebrin function at the synapse.
Functional Domain Analysis Of The Actin Binding Protein Drebrin And Its Role In The Regulation Of Neuritogenesis
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Author : Sara Geraldo
language : en
Publisher:
Release Date : 2009
Functional Domain Analysis Of The Actin Binding Protein Drebrin And Its Role In The Regulation Of Neuritogenesis written by Sara Geraldo and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009 with Microtubules categories.
Combined Effects Of Drebrin A And Mdia2 Formin On Actin Nucleation Elongation And Bundling
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Author : Anush Aram Ginosyan
language : en
Publisher:
Release Date : 2017
Combined Effects Of Drebrin A And Mdia2 Formin On Actin Nucleation Elongation And Bundling written by Anush Aram Ginosyan and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with categories.
Actin cytoskeleton is important for neuronal morphology and function. Many accessory proteins, including brain-specific drebrin A and diaphanous family of formins (mDia), regulate actin dynamics in neuronal substructures, such as dendritic spines. In order to probe for possible interrelation of drebrin and mDia2 formin, we examined their combined effects on actin polymerization, bundling, and binding. We identified drebrin A as a new interacting partner of mDia2 formin. Our results suggest two sites of interaction between drebrin A and mDia2, with the C-terminal region of drebrin binding to formin's FH2 domain and the "actin binding core" of drebrin binding to formin's C-terminal "tails." We found that drebrin A inhibits mDia2-driven actin nucleation without affecting the rate of its processive elongation. Drebrin also abolishes actin bundling mediated by FH2 domain of mDia2. Thus, our data contribute to the mechanistic understanding of actin regulation and its role in neuronal function and development.
Drebrin Preserves Endothelial Integrity By Stabilizing Nectin At Adherens Junctions
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Author :
language : en
Publisher:
Release Date : 2013
Drebrin Preserves Endothelial Integrity By Stabilizing Nectin At Adherens Junctions written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013 with categories.
The Actin Binding Protein Drebrin And Its Implications For Alzheimer S Disease Using The Model Organism C Elegans
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Author : Christian Gallrein
language : en
Publisher:
Release Date : 2020
The Actin Binding Protein Drebrin And Its Implications For Alzheimer S Disease Using The Model Organism C Elegans written by Christian Gallrein and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020 with categories.
The Role Of Fascin And Drebrin In Neuroblast Migration In The Postnatal Brain
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Author :
language : en
Publisher:
Release Date : 2014
The Role Of Fascin And Drebrin In Neuroblast Migration In The Postnatal Brain written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014 with categories.
Depletion of drebrin using different RNAi approaches affects neuroblast morphology and impairs neuroblast migration both in vitro and in vivo. Drebrin phosphorylation on Ser142 by CdkS promotes actin bundling and microtubule binding. Electroporation of phosphomimetic (S142D) or non-phosphorylatable (S142A) drebrin followed by time-lapse imaging shows decreased neuroblast migration compared to control. Our findings demonstrate that drebrin is necessary for efficient neuroblast migration and suggest that its phosphorylation on Ser142 plays an important role in regulating neuroblast orientation along the RMS.
The Role Of Denbrin In Dendritic Spine Morphology And Synaptic Function
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Author : Louise Kay
language : en
Publisher:
Release Date : 2010
The Role Of Denbrin In Dendritic Spine Morphology And Synaptic Function written by Louise Kay and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with Dendrites categories.