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Ethosuximide: Subunit- and Gβγ-dependent blocker and reporter of allosteric changes in GIRK channels.
Br J Pharmacol
January 2025
Department of Physiology and Pharmacology, School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Background And Purpose: The antiepileptic drug ethosuximide (ETX) suppresses epileptiform activity in a mouse model of GNB1 syndrome, caused by mutations in Gβ protein, likely through the inhibition of G-protein gated K (GIRK) channels. Here, we investigated the mechanism of ETX inhibition (block) of different GIRKs.
Experimental Approach: We studied ETX inhibition of GIRK channels expressed in Xenopus oocytes with or without their physiological activator, the G protein subunit dimer Gβγ.
Mechanistic origins of temperature scaling in the early embryonic cell cycle.
bioRxiv
December 2024
Laboratory of Dynamics in Biological Systems, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat, 49, Leuven, Belgium.
Temperature profoundly impacts organismal physiology and ecological dynamics, particularly affecting ectothermic species and making them especially vulnerable to climate changes. Although complex physiological processes usually involve dozens of enzymes, empirically it is found that the rates of these processes often obey the Arrhenius equation, which was originally derived for single-enzyme-catalyzed reactions. Here we have examined the temperature scaling of the early embryonic cell cycle, with the goal of understanding why the Arrhenius equation approximately holds and why it breaks down at temperature extremes.
View Article and Find Full Text PDFEvolutionary study and structural basis of proton sensing by Mus GPR4 and Xenopus GPR4.
Cell
December 2024
Key Laboratory Experimental Teratology of the Ministry of Education, New Cornerstone Science Laboratory, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, China; NHC Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Advanced Medical Research Institute, Shandong University, Jinan, China; Department of Physiology and Pathophysiology, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China. Electronic address:
Animals have evolved pH-sensing membrane receptors, such as G-protein-coupled receptor 4 (GPR4), to monitor pH changes related to their physiology and generate adaptive reactions. However, the evolutionary trajectory and structural mechanism of proton sensing by GPR4 remain unresolved. Here, we observed a positive correlation between the optimal pH of GPR4 activity and the blood pH range across different species.
View Article and Find Full Text PDFOpposing roles for Bmp signalling during the development of electrosensory lateral line organs.
Elife
January 2025
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
The lateral line system enables fishes and aquatic-stage amphibians to detect local water movement via mechanosensory hair cells in neuromasts, and many species to detect weak electric fields via electroreceptors (modified hair cells) in ampullary organs. Both neuromasts and ampullary organs develop from lateral line placodes, but the molecular mechanisms underpinning ampullary organ formation are understudied relative to neuromasts. This is because the ancestral lineages of zebrafish (teleosts) and (frogs) independently lost electroreception.
View Article and Find Full Text PDFImaging-based quantitative assessment of biomolecular condensates in vitro and in cells.
J Biol Chem
December 2024
European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address:
The formation of biomolecular condensates contributes to intracellular compartmentalization and plays an important role in many cellular processes. The characterization of condensates is however challenging, requiring advanced biophysical or biochemical methods that are often less suitable for in vivo studies. A particular need for easily accessible yet thorough methods that enable the characterization of condensates across different experimental systems thus remains.
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