Biology subjects

Bathe-Peters, M.

Publications and source records attributed to Bathe-Peters, M..

3 recordsLinked to original sources

bioRxiv2025

Effects of altered gravity on adrenergic-mediated cAMP signalling in intact cells

Spaceflight-induced cardiac atrophy and rhythm disorders are linked to dysregulation of the adrenergic-cAMP-PKA pathway. Gravity-dependent alterations in adrenergic signaling, particularly cAMP dynamics, remain poorly understood. Using fluorescence biosensors, we studied intact cells under simulated microgravity and hypergravity. We observed shifts in the EC50 of cAMP production: leftward under hypergravity and rightward in microgravity, with faster cAMP accumulation kinetics in hypergravity. Cytoskeletal remodelling, hypothesized to be a determinant of such chances, was negligible, suggesting alternative mechanisms. These findings highlight significant gravity-induced offsets in the pharmacology of a prototypical GPCR, with implications not only for adrenergic signalling but also for other pathways of pharmacological interest, potentially informing countermeasures for astronaut health and pharmacology in altered gravity settings.

cell biology↗

bioRxiv2023

Cell swelling enhances GPCR ternary complex formation, underpinning the potentiation of beta2 adrenergic receptor-mediated cAMP response

G protein-coupled receptors conformational landscape can be affected by their local, microscopic interactions within the cell plasma membrane. We employ here a pleiotropic stimulus, namely osmotic swelling, to alter the cortical environment within intact cells and monitor the response in terms of receptor function and downstream signaling. We observe that in osmotically swollen cells the {beta}2-adrenergic receptor, a prototypical GPCR, favors an active conformation, resulting in cAMP transient responses to adrenergic stimulation that have increased amplitude. The results are validated in primary cell types such as adult cardiomyocytes, a model system where swelling occurs upon ischemia-reperfusion injury. Our results suggest that receptors function is finely modulated by their biophysical context, and specifically that osmotic swelling acts as a potentiator of downstream signaling, not only for the {beta}2-adrenergic receptor, but also for other receptors, hinting at a more general regulatory mechanism.

cell biology↗

bioRxiv2022

Fluorescence spectroscopy of low-level endogenous β-Adrenergic Receptor expression at the plasma membrane of differentiating human iPSC-derived cardiomyocytes

The potential of human induced pluripotent stem cells (hiPSCs) to be differentiated into cardiomyocytes (CMs) mimicking the adult CMs functional morphology, marker genes and signaling characteristics has been investigated since over a decade. The evolution of the membrane localization of CM-specific G protein-coupled receptors throughout differentiation has received, however, only limited attention to date. We employ here advanced fluorescent spectroscopy, namely linescan Fluorescence Correlation Spectroscopy (FCS), to observe how the plasma membrane abundance of the {beta}1- and {beta}2-adrenergic receptors ({beta}1/2-ARs), labelled using a bright and photostable fluorescent antagonist, evolves during long-term monolayer culture of hiPSC-derived CMs. We compare it to the kinetic of observed mRNA levels in wildtype (WT) hiPSCs and in two CRISPR/Cas9 knock-in clones. We conduct these observations against the backdrop of our recent report that {beta}2-ARs, as opposed to {beta}1-ARs, specifically segregate to the T-Tubular system of adult CMs.

developmental biology↗