Optical Mapping of cAMP Signaling at the Nanometer Scale

Böck, Andreas; Annibale, Paolo; Kayser, Charlotte; Hannawacker, Annette; Anton, Selma E.; Maiellaro, Isabella; Zabel, Ulrike; Sivaramakrishnan, Sivaraj; Falcke, Martin

doi:10.1016/j.cell.2021.04.043

Cited by 27 publications

(36 citation statements)

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“…Direct demonstration of the TAG model would require tracking locally deposited and exceedingly transient chemical modifications of diffusing proteins in live cells. Although local gradients of a small molecule in vivo have been measured (Bock et al 2021), detecting a PTM gradient would require new technological developments. Nevertheless, TAG makes some predictions that differentiate it from other models.…”

Section: Discussionmentioning

confidence: 99%

The transcription factor activity gradient (TAG) model: contemplating a contact-independent mechanism for enhancer–promoter communication

et al. 2021

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How distal cis-regulatory elements (e.g., enhancers) communicate with promoters remains an unresolved question of fundamental importance. Although transcription factors and cofactors are known to mediate this communication, the mechanism by which diffusible molecules relay regulatory information from one position to another along the chromosome is a biophysical puzzle—one that needs to be revisited in light of recent data that cannot easily fit into previous solutions. Here we propose a new model that diverges from the textbook enhancer–promoter looping paradigm and offer a synthesis of the literature to make a case for its plausibility, focusing on the coactivator p300.

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Section: Discussionmentioning

confidence: 99%

The transcription factor activity gradient (TAG) model: contemplating a contact-independent mechanism for enhancer–promoter communication

et al. 2021

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“…Instead, signaling elements such as cAMP and calcium are typically distributed in different parts over several subcellular compartments. Indeed, recent developments in cAMP signaling have highlighted the existence of nanodomains, although still from a canonical signaling pathway point of view [25,26]. Moreover, these signaling elements also interact with different pathways (e.g., the cAMP-cGMP crosstalk) and form hybrid domains…”

Section: From Phenotype and Symptom To Endotype And Causementioning

confidence: 99%

Network pharmacology: curing causal mechanisms instead of treating symptoms

Nogales

Mamdouh

List

et al. 2022

Trends in Pharmacological Sciences

534

227

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“…Recently, two studies identified such mechanisms for the establishment of cAMP nanodomains. Bock et al (2020) observed ‘buffered diffusion’ of cAMP via cAMP‐binding sites, whereas J. Z. Zhang et al (2020) found that PKA regulatory subunits assemble liquid droplets to further localise cAMP signalling.…”

Section: In‐cell Compartmentation Versus Cell‐to‐cell Variability Of ...mentioning

confidence: 99%

Visualising and understanding cGMP signals in the cardiovascular system

Feil

Lehners

Stehle

et al. 2021

British J Pharmacology

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cGMP is an important signalling molecule in humans. Fluorescent cGMP biosensors have emerged as powerful tools for the sensitive analysis of cGMP pathways at the single-cell level. Here, we briefly outline cGMP's multifaceted role in (patho)physiology and pharmacotherapy. Then we summarise what new insights cGMP imaging has provided into endogenous cGMP signalling and drug action, with a focus on the cardiovascular system. Indeed, the use of cGMP biosensors has led to several conceptual advances, such as the discovery of local, intercellular and mechanosensitive cGMP signals. Importantly, single-cell imaging can provide valuable information about the heterogeneity of cGMP signals within and between individual cells of an isolated cell population or tissue. We also discuss current challenges and future directions of cGMP imaging, such as the direct visualisation of cGMP microdomains, simultaneous monitoring of cGMP and other signalling molecules and, ultimately, cGMP imaging in tissues and animals under close-to-native conditions.

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Optical Mapping of cAMP Signaling at the Nanometer Scale

Cited by 27 publications

References 0 publications

The transcription factor activity gradient (TAG) model: contemplating a contact-independent mechanism for enhancer–promoter communication

The transcription factor activity gradient (TAG) model: contemplating a contact-independent mechanism for enhancer–promoter communication

Network pharmacology: curing causal mechanisms instead of treating symptoms

Visualising and understanding cGMP signals in the cardiovascular system

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