The Crac Channel
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The Crac Channel
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Author : Aubin Penna
language : en
Publisher:
Release Date : 2018
The Crac Channel written by Aubin Penna and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with Biochemistry categories.
This volume discusses the cellular and molecular techniques used to study and characterize the different components of the CRAC channel signaling pathway. The chapters in this book cover topics such as fluorescence-based measurements of the CRAC channel activity in cell populations; patch-clamp recording of the CRAC channel in STIM-Orai overexpressing cells and native systems; western-blotting and co-immunoprecipitation of endogenous STIM/ORAI and protein partners; shRNA-mediated gene silencing; and the SC-SMD system. Written in the highly successful Methods in Molecular Biology 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. Thorough and cutting-edge, The CRAC Channel: Methods and Protocols is a valuable resource for any researcher interested in learning more about the CRAC channel, as its activation mechanism and roles in cellular functions have yet to be completely explored.
The Crac Channel
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Author : Aubin Penna
language : en
Publisher: Humana
Release Date : 2019-09-24
The Crac Channel written by Aubin Penna and has been published by Humana this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-09-24 with Science categories.
This volume discusses the cellular and molecular techniques used to study and characterize the different components of the CRAC channel signaling pathway. The chapters in this book cover topics such as fluorescence-based measurements of the CRAC channel activity in cell populations; patch-clamp recording of the CRAC channel in STIM-Orai overexpressing cells and native systems; western-blotting and co-immunoprecipitation of endogenous STIM/ORAI and protein partners; shRNA-mediated gene silencing; and the SC-SMD system. Written in the highly successful Methods in Molecular Biology 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. Thorough and cutting-edge, The CRAC Channel: Methods and Protocols is a valuable resource for any researcher interested in learning more about the CRAC channel, as its activation mechanism and roles in cellular functions have yet to be completely explored.
Calcium Entry Channels In Non Excitable Cells
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Author : Juliusz Ashot Kozak
language : en
Publisher: CRC Press
Release Date : 2017-07-14
Calcium Entry Channels In Non Excitable Cells written by Juliusz Ashot Kozak and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-07-14 with Science categories.
Calcium Entry Channels in Non-Excitable Cells focuses on methods of investigating the structure and function of non-voltage gated calcium channels. Each chapter presents important discoveries in calcium entry pathways, specifically dealing with the molecular identification of store-operated calcium channels which were reviewed by earlier volumes in the Methods in Signal Transduction series. Crystallographic and pharmacological approaches to the study of calcium channels of epithelial cells are also discussed. Calcium ion is a messenger in most cell types. Whereas voltage gated calcium channels have been studied extensively, the non-voltage gated calcium entry channel genes have only been identified relatively recently. The book will fill this important niche.
Store Operated Calcium Channels
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Author :
language : en
Publisher: Academic Press
Release Date : 2013-07-24
Store Operated Calcium Channels written by and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-07-24 with Science categories.
Store-operated calcium channels are found in most animal cells and regulate many cellular functions including cell division, growth, differentiation, and cell death. This volume provides a concise and informative overview of the principles of store-operated calcium entry and the key developments in the field from researchers who have led these advances. The overall goal of the volume is to provide interested students and investigators with sufficient information to enable a broad understanding of the progress and current excitement in the field. The volume contains a wealth of information that even experienced investigators in the field will find useful. The volume provides a comprehensive overview of the mechanisms and functions of store-operated calcium channels Contributors are authoritative researchers who have produced important advances in the field The volume is well-illustrated with cartoons and data to facilitate easy comprehension of the subject
The Design Synthesis And Optimisation Of Calcium Release Activated Calcium Crac Channel Inhibitors And Mitochondrial Permeability Transition Pore Mptp Modulators Using Phenotypic Screening
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Author : Yannick Lacroix
language : en
Publisher:
Release Date : 2015
The Design Synthesis And Optimisation Of Calcium Release Activated Calcium Crac Channel Inhibitors And Mitochondrial Permeability Transition Pore Mptp Modulators Using Phenotypic Screening written by Yannick Lacroix and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015 with categories.
Several previous studies have shown that the current low success of new drug molecules reaching the market can be attributed to safety-related drug attrition. Additionally, the link between the physicochemical properties of small molecule drugs and their toxicity profile has been demonstrated. Moreover, the type of pharmacological assay used to measure the biological activity of compounds when carrying out a drug discovery effort is critical to ensure the efficacy of compounds towards modulating specific signalling pathways. Recent studies have suggested that phenotypic screening, for which a target-agnostic measure of a biological response is used to develop an assay, can be more appropriate than target-based screening when developing first-in-class small molecules in the context of under-defined biological targets. This thesis describes the efforts in improving the physicochemical properties of small molecules, using phenotypic screening, towards the identification of therapeutic agents modulating two biological targets, respectively: the calcium release-activated calcium channel and the mitochondrial permeability transition pore. CRAC channel The allergen stimulation of immune cells such as T cells and mast cells triggers the depletion of the calcium stores located in the endoplasmic reticulum, which in turn leads to an influx of calcium ions across the plasma membrane through calcium release-activated calcium (CRAC) channels. This process of store-operated calcium entry through CRAC channels is the main pathway of increasing the intracellular calcium concentration in T cells and mast cells, which controls a wide range of downstream cellular functions, such as the release of pro-inflammatory cytokines and mediators like histamine and prostaglandins. Inhibiting the ion current passing through the CRAC channel (ICRAC) could help to modulate immune inflammatory responses, and thus development of an ICRAC blocker would be of considerable clinical interest to treat conditions such as asthma. The aim of the first medicinal chemistry programme described in this thesis is to identify selective small molecule oral ICRAC inhibitors as novel agents for the treatment of asthma and other inflammatory diseases. This report describes the design, chemical synthesis and application of modern medicinal chemistry principles for the identification of novel ICRAC blockers, starting from hit molecules originating from a high throughput screen. mPTP The mitochondrial permeability transition pore (mPTP) is a voltage sensitive protein channel present in the inner membrane of mitochondria and it plays a key role in cellular apoptosis and necrosis. The exact composition of the pore is not fully elucidated, however, it is thought to be a combination of several molecular constituents. Under conditions of cellular stress, the channel transitions to a state of high conductance and becomes non-selectively permeable to a wide range of solutes which freely diffuse into the mitochondria. Additionally, proteins contained in the mitochondria, such as pro-apoptotic messengers, are released into the cytosol, which leads to cell death. The sustained opening of the mPTP is believed to be a key triggering event in the pathology of several diseases. The second part of this thesis describes the design and synthesis of small molecule modulators of the mPTP as novel agents for the treatment of diseases mediated by the opening of the mPTP.
Crac Channel Related Proteins In The Pathogenesis Of Inborn Errors Of Immunity
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Author : Laura Jane Rice
language : en
Publisher:
Release Date : 2021
Crac Channel Related Proteins In The Pathogenesis Of Inborn Errors Of Immunity written by Laura Jane Rice and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021 with categories.
Activation Of The Calcium Release Activated Calcium Channel By Stim1
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Author : Paul James Hoover
language : en
Publisher:
Release Date : 2012
Activation Of The Calcium Release Activated Calcium Channel By Stim1 written by Paul James Hoover and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with categories.
In excitable and non-excitable cells store-operated Ca2+ entry (SOCE) is a ubiquitous cellular mechanism that is critical for numerous processes such as gene expression, exocytosis, and metabolism. SOC channels are activated when stimulation of cell surface receptors initiates a signaling cascade leading to Ca2+ release from the endoplasmic reticulum (ER). ER Ca2+ release triggers activation of SOC channels in the plasma membrane (PM), the best characterized of which is the Ca2+ release-activated Ca2+ (CRAC) channel. An ER embedded protein, STIM1, acts as the ER Ca2+ sensor, and a tetramer of Orai1 subunits forms the pore of the active CRAC channel. After store depletion, STIM1 and Orai1 redistribute to sites of close apposition between the ER and the PM known as ER-PM junctions where they interact to produce Ca2+ entry. However, the fundamental question of how they interact to elicit Ca2+ entry was unknown. In our first line of inquiry, we show that the C-terminal polybasic domain of STIM1 targets STIM1 to ER-PM junctions independently of Orai1, that a cytosolic region of STIM1--CRAC activation domain (CAD)--binds directly to Orai1, that CAD is necessary and sufficient to cluster and activate CRAC channels, and that clustering and activation are functionally separable events. These results support a two-part diffusion trap mechanism for SOCE. After store depletion, STIM1 forms puncta independently of Orai1 underneath the PM where CAD is positioned to trap diffusing CRAC channels in the PM and induce a conformational change to activate channels. In the second line of inquiry we address the stoichiometric requirements for CRAC channel trapping and activation at ER-PM junctions. For this we developed a novel technique in single cells to control and measure the STIM1-Orai1 stoichiometry at ER-PM junctions while simultaneously recording channel activity. We find that binding of 1-2 STIM1s is sufficient to immobilize the tetrameric CRAC channel at ER-PM junctions but this fails to evoke significant activation, while binding of 8 STIM1s causes maximal CRAC channel activity. We also find that the extent of fast Ca2+-dependent inactivation parallels STIM1-CRAC channel stoichiometry. The data are well described by a modified Monod-Wyman-Changeux model where STIM1 binds to Orai1 with negative cooperativity and channels open with positive cooperativity due to stabilization of the open state by STIM1. These results suggest a highly nonlinear dependence of CRAC channel activation on STIM:Orai stoichiometry.
Voltage Gated Calcium Channels
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Author : Gerald Werner Zamponi
language : en
Publisher: Springer Nature
Release Date : 2022-11-07
Voltage Gated Calcium Channels written by Gerald Werner Zamponi and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-11-07 with Science categories.
This book covers the tremendous progress in the current understanding of the molecular physiology of voltage-gated calcium channels. This book includes unparalleled insights into structural features of calcium channels due to X-ray crystallography and cryo-EM, which in turn yielded critical information into how these channels function under normal and pathophysiological conditions, and how they interact with calcium channel therapeutics. The chapters investigate how, with the advent of high throughput genome sequencing, numerous mutations in various calcium channel genes have been identified in patients with neurological, cardiovascular, neuropsychiatric and other disorders. This is further complemented through a much larger in vivo toolkit such as knock-out and knock-in mice. The chapters further discuss the increased complexity of calcium channel physiology that arises from mRNA editing and splicing. Finally, the book also provides an overview of the updated research on calcium channel inhibitors that can be used both in vivo and in vitro, and which may serve as a spring board for new calcium channel therapeutics for human disease. Voltage-Gated Calcium Channels is useful for academic researchers at all levels in neuroscience, biophysics, cell biology and drug discovery.
The Calcium Channel Structure Function And Implications
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Author : Martin Morad
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06
The Calcium Channel Structure Function And Implications written by Martin Morad and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-06 with Medical categories.
This is the first book to summarize experimental results from the new, rapidly expanding field of research into the calcium channel in cell membrane. Calcium is an ubiquitous messenger of various cellular functions. Its fundamental role in the regulation of cardiac contractions has long been recognized. Drugs counteracting some actions of calcium ions, namely calcium antagonists, have since become essential to research. In the last decade it has been established that calcium ions reach their target intracellular system by passing through specialized calcium channels in the membrane. Recently improved experimental techniques combined with the discovery of highly specific Ca channel ligands have dramatically enlarged our knowledge of the molecular structure and function of such channels. The contributions by leading world specialists shed new light on both basic science and possible clinical implications for cardiovascular pharmacology, endocrinology and neuropharmacology.
Animal Calcium Release Activated Calcium Crac Channels Are Homologous And Derived From The Ubiquitous Cation Diffusion Facilitators
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Author : Madeleine Gundayao Matias
language : en
Publisher:
Release Date : 2008
Animal Calcium Release Activated Calcium Crac Channels Are Homologous And Derived From The Ubiquitous Cation Diffusion Facilitators written by Madeleine Gundayao Matias and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008 with categories.
We investigated the evolutionary origins of the Ca2 Release-Activated Ca2 (CRAC) Orai channel proteins of animals and the ubiquitous Cation Diffusion Facilitator (CDF) carrier proteins. CDF antiporters derived from a primordial 2 transmembrane spanner (TMS) hairpin structure by intragenic triplication to yield 6 TMS proteins. Surprisingly, members of the CDF family proved to be homologous to members of the 4 TMS Orai channel proteins. We provide evidence that CRAC channels derived from CDF carriers by loss of the first two TMSs of the latter. Thus, TMSs 3-6 in CDF carriers are homologous to TMSs 1-4 in CRAC channels. The former probably gave rise to the latter. This is an unusual example of how a functionally and structurally more complex protein may have predated a simpler one. CRAC channels were thought to be derived exclusively from animals but we have identified new Orai channel proteins which include the choanoflagellate. Interestingly, a Stim homologue was identified in the choanoflagellate but not in green algae. Domain and motif analysis reveals several conserved regions between Orai proteins that are likely to be of functional significance.