[PDF] Mechanisms Of Capacitative And Non Capacitative Calcium Entry eBook

Author : Juan A. Rosado
Publisher : Springer
Page : 469 pages
File Size : 11,96 MB
Release : 2016-05-09
Category : Science
ISBN : 3319269747

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Calcium entry pathways in non-excitable cells presents a concise synthesis of thoughtfully selected topics covering from the different calcium entry mechanisms in non-excitable cells to the cellular microdomains and organelles regulating the calcium entry process. Particular attention is given to the fascinating group of ion channels involved in different calcium entry pathways as well as the emerging role of these channels in human disease. Calcium entry is an essential mechanism for cellular function in non-excitable cells. In general, two main calcium entry pathways exist in non-excitable cells: one pathway, named store-operated calcium entry (SOCE) requires store depletion and the second pathway is regulated by receptor occupation, but independently on calcium store depletion. The search for the molecular components of calcium entry has identified the stromal interaction molecule 1 (STIM1), as the calcium sensor of the intracellular calcium stores, and Orai as well as TRP channels as the calcium-permeable channels located in the plasma membrane. The location, interactions and function of these channels are finely regulated by a number of scaffolding proteins, membrane microdomains and cellular organelles that fine tune the amount of calcium entering the cell. Cutting-edge and user-friendly, this volume presents relevant background information, critical analysis of the current observations and directions for future research. The book is intended for basic scientists specializing in cellular biology or ion transport, as well as for biomedical researchers.

Author : Juliusz Ashot Kozak
Publisher : CRC Press
Page : 343 pages
File Size : 10,17 MB
Release : 2017-07-14
Category : Science
ISBN : 149875273X

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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.

Author : Chun-Kit Benjamin Tong
Publisher : Open Dissertation Press
Page : pages
File Size : 34,91 MB
Release : 2017-01-27
Category :
ISBN : 9781361346532

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This dissertation, "Molecular Mechanism of Disrupted Capacitative Calcium Entry in Familial Alzheimer's Disease" by Chun-kit, Benjamin, Tong, 唐俊傑, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Presenilin (PS) is the catalytic subunit of the gamma-secretase which is responsible for the cleavage of amyloid precursor protein to form beta amyloid (Aβ). Mutations in PS cause familial Alzheimer's disease (FAD) by increasing the Aβ plaques formation in the brain and thereby induce neurodegeneration. Apart from this, FAD-linked PS mutations have been demonstrated to disrupt cellular calcium (Ca2+) homeostasis. Ca2+is a vital secondary messenger that involved in various neurophysiological functions, including memory, learning, and neuroplasticity and mounting evidence suggesting that Ca2+dysregulation associated with PS mutations may play a proximal role in the AD pathogenesis. Yet, the molecular mechanism for Ca2+dysregulation in AD remains debatable. It has been reported that cellular Ca2+homeostatsis can be disrupted in various ways. On the one hand, mutant PS has been demonstrated to exaggerate Ca2+release from the endoplasmic reticulum (ER) through different pathways. On the other hand, attenuatedCa2+influx from the extracellular medium through the capacitative Ca2+entry (CCE) pathway has also been reported to bring about cellular Ca2+disruption. However, the molecular mechanism for the PS mutation-mediated CCE deficits is largely unknown. For this reason, the objective of the current study is to elucidate the underlying molecular mechanism for attenuated CCE in AD. In this study, human neuronal cell line SH-SY5Y is employed as a cellular model to investigate the effect of wild-type or FAD-linked PS1 mutation on CCE pathway. Using single cell Ca2+imaging technique, significant CCE deficits was observed in SH-SY5Y stably expressing FAD-linked PS1mutation, PS1M146L. Interestingly, this CCE attenuation in PS1 mutant expressing cells was not mediated by the down-regulation of STIM1 and Orai1 expression, the known essential molecular players in the CCE pathway. Instead, co-immunoprecipitation and proximity ligation assay have suggested a physical interaction between PS1 and STIM1 proteins. Moreover, a putative gamma-secretase mediated STIM1 cleavage was discovered by western blotting. In addition, confocal imaging showed that PS1M146L significantlyreduceSTIM1 puncta formation and ER translocation followed by the activation of CCE pathway by ER Ca2+store depletion with thapsigargin. This indicated that mutant PS1 attenuates CCE by affecting STIM1 oligomerization or its recruitment with Orai1. Taken together, our results suggested the negative regulatory role of PS on CCE pathway and hypothesized the molecular mechanism of CCE where FAD-linked PS mutation is perceived as a gain-of-function mutation and enhanced the negative impact on STIM1 to inhibit Ca2+entry.This hypothetic model provides new insights into the molecular regulation for CCE pathway and the identification of the interacting domains between PS1 and STIM1 may suggest novel targets for the development of therapeutic agents that help to treat the disease. DOI: 10.5353/th_b5186500 Subjects: Cellular signal transduction Intracellular calcium Alzheimer's disease - Molecular aspects

Author :
Publisher : Academic Press
Page : 307 pages
File Size : 30,88 MB
Release : 2013-07-24
Category : Science
ISBN : 0124079385

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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