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Endoplasmic Reticulum‐Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling

In eukaryotic cells, ultimate specificity in activation and action—for example, by means of second messengers—of the myriad of signaling cascades is primordial. In fact, versatile and ubiquitous second messengers, such as calcium (Ca(2+)) and cyclic adenosine monophosphate (cAMP), regulate multiple—...

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Autores principales: Crul, Tim, Maléth, József
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124356/
https://www.ncbi.nlm.nih.gov/pubmed/33946838
http://dx.doi.org/10.3390/ijms22094703
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author Crul, Tim
Maléth, József
author_facet Crul, Tim
Maléth, József
author_sort Crul, Tim
collection PubMed
description In eukaryotic cells, ultimate specificity in activation and action—for example, by means of second messengers—of the myriad of signaling cascades is primordial. In fact, versatile and ubiquitous second messengers, such as calcium (Ca(2+)) and cyclic adenosine monophosphate (cAMP), regulate multiple—sometimes opposite—cellular functions in a specific spatiotemporal manner. Cells achieve this through segregation of the initiators and modulators to specific plasma membrane (PM) subdomains, such as lipid rafts and caveolae, as well as by dynamic close contacts between the endoplasmic reticulum (ER) membrane and other intracellular organelles, including the PM. Especially, these membrane contact sites (MCSs) are currently receiving a lot of attention as their large influence on cell signaling regulation and cell physiology is increasingly appreciated. Depletion of ER Ca(2+) stores activates ER membrane STIM proteins, which activate PM-residing Orai and TRPC Ca(2+) channels at ER–PM contact sites. Within the MCS, Ca(2+) fluxes relay to cAMP signaling through highly interconnected networks. However, the precise mechanisms of MCS formation and the influence of their dynamic lipid environment on their functional maintenance are not completely understood. The current review aims to provide an overview of our current understanding and to identify open questions of the field.
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spelling pubmed-81243562021-05-17 Endoplasmic Reticulum‐Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling Crul, Tim Maléth, József Int J Mol Sci Review In eukaryotic cells, ultimate specificity in activation and action—for example, by means of second messengers—of the myriad of signaling cascades is primordial. In fact, versatile and ubiquitous second messengers, such as calcium (Ca(2+)) and cyclic adenosine monophosphate (cAMP), regulate multiple—sometimes opposite—cellular functions in a specific spatiotemporal manner. Cells achieve this through segregation of the initiators and modulators to specific plasma membrane (PM) subdomains, such as lipid rafts and caveolae, as well as by dynamic close contacts between the endoplasmic reticulum (ER) membrane and other intracellular organelles, including the PM. Especially, these membrane contact sites (MCSs) are currently receiving a lot of attention as their large influence on cell signaling regulation and cell physiology is increasingly appreciated. Depletion of ER Ca(2+) stores activates ER membrane STIM proteins, which activate PM-residing Orai and TRPC Ca(2+) channels at ER–PM contact sites. Within the MCS, Ca(2+) fluxes relay to cAMP signaling through highly interconnected networks. However, the precise mechanisms of MCS formation and the influence of their dynamic lipid environment on their functional maintenance are not completely understood. The current review aims to provide an overview of our current understanding and to identify open questions of the field. MDPI 2021-04-29 /pmc/articles/PMC8124356/ /pubmed/33946838 http://dx.doi.org/10.3390/ijms22094703 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Crul, Tim
Maléth, József
Endoplasmic Reticulum‐Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling
title Endoplasmic Reticulum‐Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling
title_full Endoplasmic Reticulum‐Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling
title_fullStr Endoplasmic Reticulum‐Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling
title_full_unstemmed Endoplasmic Reticulum‐Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling
title_short Endoplasmic Reticulum‐Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling
title_sort endoplasmic reticulum‐plasma membrane contact sites as an organizing principle for compartmentalized calcium and camp signaling
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124356/
https://www.ncbi.nlm.nih.gov/pubmed/33946838
http://dx.doi.org/10.3390/ijms22094703
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