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  1. Book: cAMP signaling

    Zaccolo, Manuela

    methods and protocols

    (Methods in molecular biology ; 2483 ; Springer protocols)

    2022  

    Author's details edited by Manuela Zaccolo
    Series title Methods in molecular biology ; 2483
    Springer protocols
    Collection
    Keywords Cyclic AMP ; A Kinase Anchor Proteins ; Cyclic AMP-Dependent Protein Kinases ; Fluorescence Resonance Energy Transfer ; Signal Transduction ; Second messengers (Biochemistry)/Research/Methodology ; Protein-protein interactions/Research/Methodology
    Subject code 572.696
    Language English
    Size xii, 369 Seiten, Illustrationen, 26 cm
    Edition Second edition
    Publisher Humana Press
    Publishing place New York, NY
    Publishing country United States
    Document type Book
    HBZ-ID HT021298022
    ISBN 978-1-0716-2244-5 ; 9781071622452 ; 1-0716-2244-7 ; 1071622455
    Database Catalogue ZB MED Medicine, Health

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  2. Book: cAMP signaling

    Zaccolo, Manuela

    methods and protocols

    (Methods in molecular biology ; 1294 ; Springer protocols)

    2015  

    Author's details ed. by Manuela Zaccolo
    Series title Methods in molecular biology ; 1294
    Springer protocols
    Collection
    Keywords Cyclic AMP ; A Kinase Anchor Proteins ; Cyclic AMP-Dependent Protein Kinases ; Fluorescence Resonance Energy Transfer ; Signal Transduction
    Language English
    Size X, 222 S. : Ill., graph. Darst.
    Publisher Humana Press
    Publishing place New York u.a.
    Publishing country United States
    Document type Book
    HBZ-ID HT018614258
    ISBN 978-1-4939-2536-0 ; 9781493925377 ; 1-4939-2536-9 ; 1493925377
    Database Catalogue ZB MED Medicine, Health

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  3. Article: Investigating G-protein coupled receptor signalling with light-emitting biosensors.

    Demby, Alexander / Zaccolo, Manuela

    Frontiers in physiology

    2024  Volume 14, Page(s) 1310197

    Abstract: G protein-coupled receptors (GPCRs) are the most frequent target of currently approved drugs and play a central role in both physiological and pathophysiological processes. Beyond the canonical understanding of GPCR signal transduction, the importance of ...

    Abstract G protein-coupled receptors (GPCRs) are the most frequent target of currently approved drugs and play a central role in both physiological and pathophysiological processes. Beyond the canonical understanding of GPCR signal transduction, the importance of receptor conformation, beta-arrestin (β-arr) biased signalling, and signalling from intracellular locations other than the plasma membrane is becoming more apparent, along with the tight spatiotemporal compartmentalisation of downstream signals. Fluorescent and bioluminescent biosensors have played a pivotal role in elucidating GPCR signalling events in live cells. To understand the mechanisms of action of the GPCR-targeted drugs currently available, and to develop new and better GPCR-targeted therapeutics, understanding these novel aspects of GPCR signalling is critical. In this review, we present some of the tools available to interrogate each of these features of GPCR signalling, we illustrate some of the key findings which have been made possible by these tools and we discuss their limitations and possible developments.
    Language English
    Publishing date 2024-01-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2023.1310197
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: cAMP Buffering via Liquid-Liquid Phase Separation.

    Zaccolo, Manuela

    Function (Oxford, England)

    2020  Volume 2, Issue 1, Page(s) zqaa048

    Language English
    Publishing date 2020-12-26
    Publishing country England
    Document type Editorial
    ISSN 2633-8823
    ISSN (online) 2633-8823
    DOI 10.1093/function/zqaa048
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Compartmentalised cAMP signalling in the primary cilium.

    Paolocci, Ester / Zaccolo, Manuela

    Frontiers in physiology

    2023  Volume 14, Page(s) 1187134

    Abstract: cAMP is a universal second messenger that relies on precise spatio-temporal regulation to control varied, and often opposing, cellular functions. This is achieved via selective activation of effectors embedded in multiprotein complexes, or signalosomes, ... ...

    Abstract cAMP is a universal second messenger that relies on precise spatio-temporal regulation to control varied, and often opposing, cellular functions. This is achieved via selective activation of effectors embedded in multiprotein complexes, or signalosomes, that reside at distinct subcellular locations. cAMP is also one of many pathways known to operate within the primary cilium. Dysfunction of ciliary signaling leads to a class of diseases known as ciliopathies. In Autosomal Dominant Polycystic Kidney Disease (ADPKD), a ciliopathy characterized by the formation of fluid-filled kidney cysts, upregulation of cAMP signaling is known to drive cystogenesis. For decades it has been debated whether the primary cilium is an independent cAMP sub-compartment, or whether it shares a diffusible pool of cAMP with the cell body. Recent studies now suggest it is a specific pool of cAMP generated in the cilium that propels cyst formation in ADPKD, supporting the notion that this antenna-like organelle is a compartment within which cAMP signaling occurs independently from cAMP signaling in the bulk cytosol. Here we present examples of cAMP function in the cilium which suggest this mysterious organelle is home to more than one cAMP signalosome. We review evidence that ciliary membrane localization of G-Protein Coupled Receptors (GPCRs) determines their downstream function and discuss how optogenetic tools have contributed to establish that cAMP generated in the primary cilium can drive cystogenesis.
    Language English
    Publishing date 2023-05-09
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2023.1187134
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Regulation of cardiac function by cAMP nanodomains.

    Folkmanaite, Milda / Zaccolo, Manuela

    Bioscience reports

    2023  Volume 43, Issue 2

    Abstract: Cyclic adenosine monophosphate (cAMP) is a diffusible intracellular second messenger that plays a key role in the regulation of cardiac function. In response to the release of catecholamines from sympathetic terminals, cAMP modulates heart rate and the ... ...

    Abstract Cyclic adenosine monophosphate (cAMP) is a diffusible intracellular second messenger that plays a key role in the regulation of cardiac function. In response to the release of catecholamines from sympathetic terminals, cAMP modulates heart rate and the strength of contraction and ease of relaxation of each heartbeat. At the same time, cAMP is involved in the response to a multitude of other hormones and neurotransmitters. A sophisticated network of regulatory mechanisms controls the temporal and spatial propagation of cAMP, resulting in the generation of signaling nanodomains that enable the second messenger to match each extracellular stimulus with the appropriate cellular response. Multiple proteins contribute to this spatiotemporal regulation, including the cAMP-hydrolyzing phosphodiesterases (PDEs). By breaking down cAMP to a different extent at different locations, these enzymes generate subcellular cAMP gradients. As a result, only a subset of the downstream effectors is activated and a specific response is executed. Dysregulation of cAMP compartmentalization has been observed in cardiovascular diseases, highlighting the importance of appropriate control of local cAMP signaling. Current research is unveiling the molecular organization underpinning cAMP compartmentalization, providing original insight into the physiology of cardiac myocytes and the alteration associated with disease, with the potential to uncover novel therapeutic targets. Here, we present an overview of the mechanisms that are currently understood to be involved in generating cAMP nanodomains and we highlight the questions that remain to be answered.
    MeSH term(s) Cyclic AMP/metabolism ; Second Messenger Systems/physiology ; Signal Transduction/physiology ; Myocytes, Cardiac/metabolism ; Phosphoric Diester Hydrolases
    Chemical Substances Cyclic AMP (E0399OZS9N) ; Phosphoric Diester Hydrolases (EC 3.1.4.-)
    Language English
    Publishing date 2023-02-07
    Publishing country England
    Document type Review ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 764946-0
    ISSN 1573-4935 ; 0144-8463
    ISSN (online) 1573-4935
    ISSN 0144-8463
    DOI 10.1042/BSR20220953
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Compartmentalized cAMP signalling and control of cardiac rhythm.

    Tomek, Jakub / Zaccolo, Manuela

    Philosophical transactions of the Royal Society of London. Series B, Biological sciences

    2023  Volume 378, Issue 1879, Page(s) 20220172

    Abstract: In the last 30 years, the field of cyclic adenosine 3',5'-monophosphate (cAMP) signalling has witnessed a transformative development with the realization that cAMP is compartmentalized and that spatial regulation of cAMP is critical for faithful signal ... ...

    Abstract In the last 30 years, the field of cyclic adenosine 3',5'-monophosphate (cAMP) signalling has witnessed a transformative development with the realization that cAMP is compartmentalized and that spatial regulation of cAMP is critical for faithful signal propagation and hormonal specificity. This recognition has changed our understanding of cAMP signalling from the canonical model, where a linear pathway connects a plasma membrane receptor to intracellular effectors and their targets, to a model where signal transduction occurs within a complex network of alternative branches and where an individual receptor leads to activation of a limited fraction of the network, enabled by local regulation of independent signalling units, resulting in a specific functional outcome. The cardiac myocyte has served as the cell model for many of the original findings leading to this paradigm. In this review, we cover some of the evidence supporting this new perspective and discuss how this model is providing novel mechanistic insight into cardiac myocyte physiology. With a focus on the regulation of cardiac rhythm, we consider how this model can provide an original framework for the identification of disease mechanisms. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.
    MeSH term(s) Cyclic AMP/metabolism ; Signal Transduction/physiology ; Myocytes, Cardiac/metabolism ; Cardiovascular Physiological Phenomena
    Chemical Substances Cyclic AMP (E0399OZS9N)
    Language English
    Publishing date 2023-05-01
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 208382-6
    ISSN 1471-2970 ; 0080-4622 ; 0264-3839 ; 0962-8436
    ISSN (online) 1471-2970
    ISSN 0080-4622 ; 0264-3839 ; 0962-8436
    DOI 10.1098/rstb.2022.0172
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Micro-2D Cell Culture for cAMP Measurements Using FRET Reporters in Human iPSC-Derived Cardiomyocytes.

    Koschinski, Andreas / Zaccolo, Manuela

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2483, Page(s) 141–165

    Abstract: In the last years human induced pluripotent stem cell-derived cardiomyocytes (hIPS-CMs) have emerged as a promising alternative to rodent-derived cardiomyocytes. However, as the differentiation process is lengthy and commercially available cells are ... ...

    Abstract In the last years human induced pluripotent stem cell-derived cardiomyocytes (hIPS-CMs) have emerged as a promising alternative to rodent-derived cardiomyocytes. However, as the differentiation process is lengthy and commercially available cells are expensive, the cell number is limited. Here we provide detailed information on how to scale down 2D cell cultures of hIPS-CMs for the purpose of cAMP FRET measurements, thereby extending the number of possible experiments by more than tenfold. Crucial factors like cell density or cell number to culturing media volume can be maintained exactly as under normal culturing conditions and existing equipment does not need to be modified.The chapter covers the preparation of downscaled cell culture vessels, coating and seeding procedures, transduction or transfection of the cells with a genetically encoded cAMP FRET sensor, performing real-time cAMP FRET measurements with this sensor and the analysis of generated imaging data. Numbers for seeding areas, seeding densities, coating volumes and concentrations, media volumes, and concentrations of reagents are given as guidelines.
    MeSH term(s) Cell Culture Techniques/methods ; Cell Differentiation ; Fluorescence Resonance Energy Transfer ; Humans ; Induced Pluripotent Stem Cells ; Myocytes, Cardiac
    Language English
    Publishing date 2022-03-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2245-2_9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: G Protein-Coupled Receptor Signaling: New Insights Define Cellular Nanodomains.

    Lohse, Martin J / Bock, Andreas / Zaccolo, Manuela

    Annual review of pharmacology and toxicology

    2023  Volume 64, Page(s) 387–415

    Abstract: G protein-coupled receptors are the largest and pharmacologically most important receptor family and are involved in the regulation of most cell functions. Most of them reside exclusively at the cell surface, from where they signal via heterotrimeric G ... ...

    Abstract G protein-coupled receptors are the largest and pharmacologically most important receptor family and are involved in the regulation of most cell functions. Most of them reside exclusively at the cell surface, from where they signal via heterotrimeric G proteins to control the production of second messengers such as cAMP and IP
    MeSH term(s) Humans ; Cell Membrane ; Signal Transduction ; Drug Development
    Language English
    Publishing date 2023-09-08
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 196587-6
    ISSN 1545-4304 ; 0362-1642
    ISSN (online) 1545-4304
    ISSN 0362-1642
    DOI 10.1146/annurev-pharmtox-040623-115054
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Using the Proteomics Toolbox to Resolve Topology and Dynamics of Compartmentalized cAMP Signaling.

    Kovanich, Duangnapa / Low, Teck Yew / Zaccolo, Manuela

    International journal of molecular sciences

    2023  Volume 24, Issue 5

    Abstract: cAMP is a second messenger that regulates a myriad of cellular functions in response to multiple extracellular stimuli. New developments in the field have provided exciting insights into how cAMP utilizes compartmentalization to ensure specificity when ... ...

    Abstract cAMP is a second messenger that regulates a myriad of cellular functions in response to multiple extracellular stimuli. New developments in the field have provided exciting insights into how cAMP utilizes compartmentalization to ensure specificity when the message conveyed to the cell by an extracellular stimulus is translated into the appropriate functional outcome. cAMP compartmentalization relies on the formation of local signaling domains where the subset of cAMP signaling effectors, regulators and targets involved in a specific cellular response cluster together. These domains are dynamic in nature and underpin the exacting spatiotemporal regulation of cAMP signaling. In this review, we focus on how the proteomics toolbox can be utilized to identify the molecular components of these domains and to define the dynamic cellular cAMP signaling landscape. From a therapeutic perspective, compiling data on compartmentalized cAMP signaling in physiological and pathological conditions will help define the signaling events underlying disease and may reveal domain-specific targets for the development of precision medicine interventions.
    MeSH term(s) Cyclic AMP ; Proteomics ; Signal Transduction/physiology ; Second Messenger Systems
    Chemical Substances Cyclic AMP (E0399OZS9N)
    Language English
    Publishing date 2023-02-28
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24054667
    Database MEDical Literature Analysis and Retrieval System OnLINE

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