Cell–cell communication: new insights and clinical implications

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 7, 2024

Multicellular organisms are composed of diverse cell types that must coordinate their behaviors through communication. Cell-cell communication (CCC) is essential for growth, development, differentiation, tissue and organ formation, maintenance, physiological regulation. Cells communicate direct contact or at a distance using ligand-receptor interactions. So cellular encompasses two processes: signal conduction generation intercellular transmission signals, transduction reception procession signals. Deciphering networks critical understanding metabolism. First, we comprehensively review the historical milestones in CCC studies, followed by detailed description mechanisms molecule importance main signaling pathways they mediate maintaining biological functions. Then systematically introduce series human diseases caused abnormalities progress clinical applications. Finally, summarize various methods monitoring interactions, including imaging, proximity-based chemical labeling, mechanical force analysis, downstream analysis strategies, single-cell technologies. These aim to illustrate how functions depend on these interactions complexity regulatory regulate crucial processes, homeostasis, immune responses diseases. In addition, this enhances our processes occur after cell-cell binding, highlighting its application discovering new therapeutic targets biomarkers related precision medicine. This collective provides foundation developing targeted drugs personalized treatments.

Язык: Английский

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The Nicotinic Acetylcholine Receptor and Its Pentameric Homologs: Toward an Allosteric Mechanism of Signal Transduction at the Atomic Level

Annual Review of Biochemistry, Год журнала: 2024, Номер 93(1), С. 339 - 366

Опубликована: Фев. 12, 2024

The nicotinic acetylcholine receptor has served, since its biochemical identification in the 1970s, as a model of an allosteric ligand-gated ion channel mediating signal transition at synapse. In recent years, application X-ray crystallography and high-resolution cryo-electron microscopy, together with molecular dynamic simulations receptors homologs, have opened new era understanding gating by neurotransmitter. They reveal, atomic resolution, diversity flexibility multiple ligand-binding sites, including recently discovered modulatory sites distinct from neurotransmitter orthosteric site, conformational dynamics activation process switch linking these sites. emerging studies paves way for pharmacology based, first, upon occurrence original mode indirect modulation, steric competition single rigid binding second, design drugs that specifically interact privileged conformations such agonists, antagonists, desensitizers. Research on is still forefront action nervous system.

Язык: Английский

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Modulation of a rapid neurotransmitter receptor-ion channel by membrane lipids

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 11

Опубликована: Янв. 11, 2024

Membrane lipids modulate the proteins embedded in bilayer matrix by two non-exclusive mechanisms: direct or indirect. The latter comprise those effects mediated physicochemical state of membrane bilayer, whereas modulation entails more specific regulatory transduced via recognition sites on target protein. nicotinic acetylcholine receptor (nAChR), paradigm member pentameric ligand-gated ion channel (pLGIC) superfamily rapid neurotransmitter receptors, is modulated both mechanisms. Reciprocally, nAChR protein exerts influence its surrounding interstitial lipids. Folding, conformational equilibria, ligand binding, permeation, topography, and diffusion are knowledge gained from biophysical studies this prototypic can be applied to other receptors most integral proteins.

Язык: Английский

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JWA inhibits nicotine-induced lung cancer stemness and progression through CHRNA5/AKT-mediated JWA/SP1/CD44 axis

Ecotoxicology and Environmental Safety, Год журнала: 2023, Номер 259, С. 115043 - 115043

Опубликована: Май 23, 2023

Cigarette smoking is an independent risk factor for lung cancer. Nicotine, as addictive substance in tobacco and e-cigarettes, known to promote tumor progression metastasis despite being a non-carcinogen. As suppressor gene, JWA widely involved the inhibition of growth maintenance cellular homeostasis, including non-small cell cancer (NSCLC). However, role nicotine-induced remains unclear. Here, we reported first time that was significantly downregulated smoking-related associated with overall survival. Nicotine exposure reduced expression dose-dependent manner. Gene Set Enrichment Analysis (GSEA) analysis showed stemness pathway enriched cancer, negatively molecules CD44, SOX2, CD133. also inhibited nicotine-enhanced colony formation, spheroid EDU incorporation cells. Mechanically, nicotine via CHRNA5-mediated AKT pathway. Lower enhanced CD44 through ubiquitination-mediated degradation Specificity Protein 1 (SP1). The vivo data indicated JAC4 JWA/SP1/CD44 axis nicotine-triggered stemness. In conclusion, down-regulating progression. Our study may provide new insights develop therapy nicotine-related cancers.

Язык: Английский

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Concurrent diffusion of nicotinic acetylcholine receptors and fluorescent cholesterol disclosed by two-colour sub-millisecond MINFLUX-based single-molecule tracking

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

Nicotinic acetylcholine receptors (nAChRs) are ubiquitous neurotransmitter predominantly located at the cell-surface of neurons and muscle cells. Their dynamics affect synaptogenesis neurodevelopmental stages efficacy synaptic transmission in adult synapse. Here we exploit enhanced capabilities superresolution fluorescence MINFLUX microscopy to track for minute-long periods with nanometric precision sub-millisecond time resolution 2D translational bungarotoxin-labelled muscle-type nAChR tandem a fluorescent cholesterol analogue. To this end, implemented multiplexing procedure continuous that enabled simultaneous excitation two molecules using single wavelength, followed by discrimination their emissions via differential ratiometric recording. Single-molecule trajectories displayed heterogeneous spectrum diffusive behaviours (subdiffusive, Brownian superdiffusive), predominance subdiffusive component, which became less pronounced upon depletion. nAChRs spent most lifetime confined areas characteristic size (~ 0.005 µm²) lasting ~ 100 ms. Further, captured regions where moved jointly, both confinement sojourns along free walks, strongly indicated mutual interactions between receptor macromolecule neutral lipid. best our knowledge, study constitutes first series experiments showing diffusion transmembrane protein -a functionally important receptor- together key membrane lipid native plasma live cell such high detail, thanks MINFLUX-based recordings.

Язык: Английский

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Exploring Alzheimer's Disease Treatment: Established Therapies and Novel Strategies for Future Care

European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177520 - 177520

Опубликована: Март 1, 2025

Язык: Английский

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Editorial: Novel insights into the modulation of protein function by lipids and membrane organization

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Апрель 24, 2025

Язык: Английский

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Nicotinic acetylcholine receptors in the brain

Handbook of clinical neurology, Год журнала: 2025, Номер unknown, С. 37 - 54

Опубликована: Янв. 1, 2025

Язык: Английский

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Allosteric Control of Super-Agonism in a Ligand-Gated Ion Channel

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 25, 2025

ABSTRACT Ligand-gated ion channels open in response to the binding of an agonist. The agonist site is typically located tens Angstroms away from channel gate, which lies within membrane and thus gating mechanism considered a classic example allostery proteins. multi-subunit nature these proteins also means that modulatory effects on process can be mediated by several other distinct regions – so called allosteric sites. One most well-studied this regard, nicotinic acetylcholine receptor. Super-agonists are compounds produce greater maximal than endogenous ligand (acetylcholine case). They able stabilize state have important consequences for neuronal signaling. Some super-agonist through orthosteric site, but others alternative latter often much harder identify depend very precisely subunit composition In work we sought TC-2559, known acts as such only at one particular combination receptors high sensitivity receptor comprised 2 alpha subunits 3 beta (as opposed low has subunits). By using advanced computational methods, supported two-voltage electrode clamp experiments, were show TC-2559 not binds unique b2-b2 interface HS exerts interactions agonists make, more importantly it induces changes support concept gain overall efficacy. Our results highlight how control exists modulate function.

Язык: Английский

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Optical soliton solutions of the coupled Radhakrishnan-Kundu-Lakshmanan equation by using the extended direct algebraic approach

Heliyon, Год журнала: 2023, Номер 9(10), С. e20852 - e20852

Опубликована: Окт. 1, 2023

The analytical soliton solutions place a lot of value on birefringent fibres. major goal this study is to generate novel forms for the Radhakrishnan-Kundu-Lakshmanan equation, which depicts unstable optical solitons that arise from propagations using (presumably new) extended direct algebraic (EDA) technique used here extract large number RKLE. It gives up thirty-seven, essentially correspond all families. This method's ability determine many sorts through single process one its key advantages. Additionally, it simple infer employed in really straightforward yet quite effective approaches solving nonlinear partial differential equations so, may be regarded as comprehensive procedure. resulting are found hyperbolic, periodic, trigonometric, bright and dark, combined bright-dark, W-shaped soliton, these visually represented by means 2D, 3D, density plots. present can investigate several other systems understand physical insights fibre.

Язык: Английский

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