16 research outputs found
Every Detail Matters. That Is, How the Interaction between Gα Proteins and Membrane Affects Their Function
In highly organized multicellular organisms such as humans, the functions of an individual cell are dependent on signal transduction through G protein-coupled receptors (GPCRs) and subsequently heterotrimeric G proteins. As most of the elements belonging to the signal transduction system are bound to lipid membranes, researchers are showing increasing interest in studying the accompanying protein–lipid interactions, which have been demonstrated to not only provide the environment but also regulate proper and efficient signal transduction. The mode of interaction between the cell membrane and G proteins is well known. Despite this, the recognition mechanisms at the molecular level and how the individual G protein-membrane attachment signals are interrelated in the process of the complex control of membrane targeting of G proteins remain unelucidated. This review focuses on the mechanisms by which mammalian Gα subunits of G proteins interact with lipids and the factors responsible for the specificity of membrane association. We summarize recent data on how these signaling proteins are precisely targeted to a specific site in the membrane region by introducing well-defined modifications as well as through the presence of polybasic regions within these proteins and interactions with other components of the heterocomplex
The Effects of Tree and Stand Traits on the Specific Leaf Area in Managed Scots Pine Forests of Different Ages
The purpose of this study was to understand the relationships between stand structure (tree size, volume, biomass, social position, stand density) and the variability of specific leaf area (SLA) at the stand level, which could improve forest management modeling. The study was carried out on 100 trees selected from 10 stands of Scots pine located in northwestern Poland. The stands had been established in a similar way and were similarly managed. Five mid-aged (51–60 years) and five mature (81–90 years) pure Scots pine stands were selected. To obtain the SLA index, we used the direct method, which involves scanning ca. 50 needles from each part of the tree crown. The average SLA was from 4.65 to 6.62 m2·kg−1 and differed significantly according to the part of the crown measured (p < 0.0001) and the tree age (p < 0.0001). The smallest SLA was in the upper part of the crown and the largest in the lower part of the crown, which is in line with the known relation to the light exposure of needles. Mid-aged stands of Scots pine have higher SLA values than mature ones. Dominant trees in mid-aged stands have a lower SLA than more shaded intermediate ones, which is probably due to the different lighting conditions within the canopy. No clear relationship is observed between the stand density and the SLA
G Protein-Coupled Receptor Dimerization—What Next?
Numerous studies highlight the therapeutic potential of G protein-coupled receptor (GPCR) heterodimers, emphasizing their significance in various pathological contexts. Despite extensive basic research and promising outcomes in animal models, the translation of GPCR heterodimer-targeting drugs into clinical use remains limited. The complexities of in vivo conditions, particularly within thecomplex central nervous system, pose challenges in fully replicating physiological environments, hindering clinical success. This review discusses examples of the most studied heterodimers, their involvement in nervous system pathology, and the available data on their potential ligands. In addition, this review highlights the intricate interplay between lipids and GPCRs as a potential key factor in understanding the complexity of cell signaling. The multifaceted role of lipids in modulating the dynamics of GPCR dimerization is explored, shedding light on the elaborate molecular mechanisms governing these interactions
The Use of Capsuled Paraffin Wax in Low-Temperature Thermal Energy Storage Applications: An Experimental and Numerical Investigation
The article deals with the experimental and numerical thermal-flow behaviours of a low-temperature Phase Change Material (PCM) used in Thermal Energy Storage (TES) industrial applications. The investigated PCM is a composition that consists of a mixture of paraffin wax capsuled in a melamine-formaldehyde membrane and water, for which a phase change process occurs within the temperature range of 4 °C to 6 °C and the maximum heat storage capacity is equal to 72 kJ/kg. To test the TES capabilities of the PCM for operating conditions close to real ones, a series of experimental tests were performed on cylindrical modules with fixed heights of 250 mm and different outer diameters of 15, 22, and 28 mm, respectively. The module was tested in a specially designed wind tunnel where the Reynolds numbers of between 15,250 to 52,750 were achieved. In addition, a mathematical model of the analysed processes, based on the enthalpy porosity method, was proposed and validated. The temperature changes during the phase transitions that were obtained from the numerical analyses in comparison with the experimental results have not exceeded 20% of the relative error for the phase change region and no more than 10% for the rest. Additionally, the PCM was examined while using a Scanning Electron Microscope (SEM), which indicated no changes in the internal structure during phase transitions and a homogeneous structure, regardless of the tested temperature ranges
Beyond the G protein α subunit: investigating the functional impact of other components of the Gαi3 heterotrimers
Abstract Background Specific interactions between G protein-coupled receptors (GPCRs) and G proteins play a key role in mediating signaling events. While there is little doubt regarding receptor preference for Gα subunits, the preferences for specific Gβ and Gγ subunits and the effects of different Gβγ dimer compositions on GPCR signaling are poorly understood. In this study, we aimed to investigate the subcellular localization and functional response of Gαi3-based heterotrimers with different combinations of Gβ and Gγ subunits. Methods Live-cell imaging microscopy and colocalization analysis were used to investigate the subcellular localization of Gαi3 in combination with Gβ1 or Gβ2 heterotrimers, along with representative Gγ subunits. Furthermore, fluorescence lifetime imaging microscopy (FLIM-FRET) was used to investigate the nanoscale distribution of Gαi3-based heterotrimers in the plasma membrane, specifically with the dopamine D2 receptor (D2R). In addition, the functional response of the system was assessed by monitoring intracellular cAMP levels and conducting bioinformatics analysis to further characterize the heterotrimer complexes. Results Our results show that Gαi3 heterotrimers mainly localize to the plasma membrane, although the degree of colocalization is influenced by the accompanying Gβ and Gγ subunits. Heterotrimers containing Gβ2 showed slightly lower membrane localization compared to those containing Gβ1, but certain combinations, such as Gαi3β2γ8 and Gαi3β2γ10, deviated from this trend. Examination of the spatial arrangement of Gαi3 in relation to D2R and of changes in intracellular cAMP level showed that the strongest functional response is observed for those trimers for which the distance between the receptor and the Gα subunit is smallest, i.e. complexes containing Gβ1 and Gγ8 or Gγ10 subunit. Deprivation of Gαi3 lipid modifications resulted in a significant decrease in the amount of protein present in the cell membrane, but did not always affect intracellular cAMP levels. Conclusion Our studies show that the composition of G protein heterotrimers has a significant impact on the strength and specificity of GPCR-mediated signaling. Different heterotrimers may exhibit different conformations, which further affects the interactions of heterotrimers and GPCRs, as well as their interactions with membrane lipids. This study contributes to the understanding of the complex signaling mechanisms underlying GPCR-G-protein interactions and highlights the importance of the diversity of Gβ and Gγ subunits in G-protein signaling pathways. Video Abstrac