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Mechanobiological Evidence for the Control of Neutrophil Activity by Fluid Shear Stress
Published in Jiro Nagatomi, Eno Essien Ebong, Mechanobiology Handbook, 2018
Hainsworth Y. Shin, Xiaoyan Zhang, Ayako Makino, Geert W. Schmid-Schönbein
The reported effects of fluid shear stress on cytosolic Rac1 and Rac2 activity in conjunction with the role of fluid flow modulation of pseudopod activity (Makino et al., 2005) implicate upstream signal transduction pathways, particularly G-protein signaling associated with GPCRs that regulate neutrophil chemotaxis (e.g., fMLP receptor, platelet activating factor [PAF] receptor). Classically, downstream signaling initiated by stimulation of transmembrane GPCRs with cytokines is dependent on their conformation within the cell membrane which is, in turn, determinant of their cytoplasmic interactions with heterotrimeric G-proteins: Gα, Gβ, and Gγ (as reviewed elsewhere Miyajima et al., 1992; Onishi et al., 1998). For the most part, selective activation of GPCRs by their respective cytokine ligands involves the inhibitory isoform of the Gα subunit, Gαi, since it attenuates downstream adenylate cyclase-mediated production of the second messenger, cyclic adenosine monophosphate (cAMP); this is one of three possible Gα subunits that plays a role in GPCR signaling with the others being Gαs and Gαq, which enhance downstream adenylate cyclase activity. The predominant involvement of Gαi in cytokine signaling is corroborated by the fact that the GPCRs participating in cytokine activation of neutrophil motility typically exhibit sensitivity to pertussis toxin, an inhibitor of Gαi.
Receptor-Based Biosensors: Focus on Olfactory Receptors and Cell-Free Sensors
Published in Yubing Xie, The Nanobiotechnology Handbook, 2012
GPCRs comprise seven hydrophobic α helices that span the plasma membrane. The intracellular C-terminus and cytoplasmic loops are involved in binding the heterotrimeric G-protein complex (α, β, and γ). The N-terminus and extracellular loops have been associated with larger ligand binding such as peptides, while smaller chemical ligands bind on sites within the transmembrane a helical core (Gether and Kobilka 1998). Upon ligand binding, the GPCR coupled to the heterotrimeric G-protein complex undergoes conformational changes that result in the activation of the a subunit by guanosine nucleotide exchange of GDP for GTP. The a subunit dissociates from the remaining protein complex to bind an effector protein, which regulates further downstream signaling events. The effector protein target is dependent on the particular G-protein subunit involved. In olfactory signaling, this Ga olf protein interacts with and activates adenylate cyclase (AC) (Spehr and Munger 2009). The cAMP levels thus rise and act on cAMP-gated cation channels, resulting in an influx of Ca2+ and Na2+. Ca2+ in turn regulates chloride (Cl−) channels, causing an efflux of Cl− and membrane depolarization. This leads to propagation of an action potential down the axon of the olfactory neuron to transmit the signal to the brain (Figure 10.1).
Plant pharmacology: Insights into in-planta kinetic and dynamic processes of xenobiotics
Published in Critical Reviews in Environmental Science and Technology, 2022
Tomer Malchi, Sara Eyal, Henryk Czosnek, Moshe Shenker, Benny Chefetz
There are numerous examples of analogies and homologies of receptors between animals and plants, and examples of such are transmembrane ion-channel receptors, transmembrane G-protein-coupled receptors and transmembrane receptors within cytosolic domains. Transmembrane ion-channel receptors such as voltage-gated ion channels regulate the ionic balance of the cell and cellular processes. Plant ion channel families exhibit homologies to animal proteins, and include hyperpolarization-and depolarization-activated Shaker-type potassium channels, chloride transporters/channels, cyclic nucleotide–gated channels, and ionotropic glutamate receptor homologs (Ward et al., 2009). Transmembrane G-protein-coupled receptors can activate a signal-transduction pathway that alters cellular processes through the activation of a second messenger system. Heterotrimeric G protein signaling regulates a wide range of growth and developmental processes in both animals and plants, but the two kingdoms are believed to have differences in protein structure, subunit composition and different G-protein-associated receptors (Stateczny et al., 2016; Trusov & Botella, 2016);