This review focuses on the self-organization of organic-inorganic hybrid materials with molecularscale and mesoscale periodicities. It describes organosilicas with molecular periodicity of organic units formed by self-organization of bissilylated organic monomers without employing templates, as well as porous organosilicas with mesoscale periodicity, i.e., periodic mesoporous organosilicas (PMOs). Moreover, PMOs with molecular-scale periodicity in the framework are discussed. Relevant uses of PMOs in diverse applications are summarized in the final chapter.
Abstract-Regulators of G protein signaling (RGS), which act as GTPase activators, are a family of cytosolic proteins emerging rapidly as an important means of controlling G protein-mediated cell signals. The importance of RGS action has been verified in vitro for various kinds of cell function. Their in situ modes of action in intact cells are, however, poorly understood. Here we show that an increase in intracellular Ca 2ϩ evoked by membrane depolarization controls the RGS action on G protein activation of muscarinic K ϩ (K G ) channel in the heart. Acetylcholine-induced K G current exhibits a slow time-dependent increase during hyperpolarizing voltage steps, referred to as "relaxation." This reflects the relief from the decrease in available K G channel number induced by cell depolarization. This phenomenon is abolished when an increase in intracellular Ca 2ϩ is prevented. It is also abolished when a calmodulin inhibitor or a mutant RGS4 is applied that can bind to calmodulin but that does not accelerate GTPase activity. Therefore, an increase in intracellular Ca 2ϩ and the resultant formation of Ca 2ϩ /calmodulin facilitate GTPase activity of RGS and thus decrease the available channel number on depolarization. These results indicate a novel and probably general pathway that Key Words:channels, which are directly activated by the ␥ subunits released from pertussis toxin-sensitive G proteins (designated G K ), contribute to acetylcholine (ACh)-induced deceleration of heartbeat and neurotransmitter-evoked slow inhibitory postsynaptic potentials in different neurons. 1-3 The cardiac K G channel is a heterotetramer composed of two kinds of inward rectifier K ϩ channel (Kir) subunits, GIRK1/Kir3.1 and GIRK4/Kir3.4, 4 which can be reconstituted by expressing the Kir subunits and m 2 -muscarinic receptors in Xenopus oocytes. The reconstituted current, however, lacks several of the characteristic features of native K G currents. One of these features is an agonist concentration-dependent slow increase at hyperpolarized potentials, which is referred to as "relaxation." 3,5 Since its first description in sinoatrial node cells, 5 the molecular mechanism underlying this characteristic feature of the K G current has remained an enigma.Recently a family of cytosolic proteins that act as regulators of G protein signaling (RGS) has been identified. 6,7 These proteins accelerate GTP hydrolysis on ␣ subunits of G i/o and/or G q , and are supposed to play essential roles in the negative regulation of various G protein-mediated cellsignaling systems. In reconstituted systems, RGS proteins have been reported to accelerate the time course of activation and deactivation of K G currents induced by agonists. 8 -10 We have shown that one RGS protein, RGS4, restores the feature of relaxation to the reconstituted K G current 11 and that this effect was mediated exclusively by the interaction of RGS domain with pertussis toxin-sensitive G␣ subunit. 12 The question of how the cytosolic RGS protein confers this membrane potential-depende...
The effects of RGS4 on the voltage‐dependent relaxation of G protein‐gated K+ (KG) channels were examined by heterologous expression in Xenopus oocytes. While the relaxation kinetics was unaffected by the acetylcholine concentration ([ACh]) in the absence of RGS4, it became dependent on [ACh] when RGS4 was co‐expressed. Kinetic analyses indicated that RGS4 confers to the KG channel a voltage‐independent inhibitory gating mechanism, which was attenuated by ACh in a concentration‐dependent fashion. In vitro biochemical studies showed that RGS4 could bind to the protein complex containing KG channel subunits. Since the native cardiac KG channel exhibited similar agonist‐dependent relaxation kinetics to that mediated by RGS4, it is suggested that KG channel gating is a novel physiological target of RGS protein‐mediated regulation.
RGS (regulators of G-protein signalling) are a diverse group of proteins, which accelerate intrinsic GTP hydrolysis on heterotrimeric G-protein a subunits. They are involved in the control of a physiological behaviour known as 'relaxation' of G-protein-gated K+ channels in cardiac myocytes. The GTPase-accelerating activity of cardiac RGS proteins, such as RGS4, is inhibited by PtdIns(3,4,5)P3 (phosphatidylinositol 3,4,5-trisphosphate) and this inhibition is cancelled by Ca2+/calmodulin (CaM) formed during membrane depolarization. G-protein-gated K+ channel activity decreases on depolarization owing to the facilitation of GTPase-activating protein activity by RGS proteins and vice versa on hyperpolarization. The molecular mechanism responsible for this reciprocal control of RGS action by PtdIns(3,4,5)P3 and Ca2+/CaM, however, has not been fully elucidated. Using lipid-protein co-sedimentation assay and surface plasmon resonance measurements, we show in the present study that the control of the GTPase-accelerating activity of the RGS4 protein is achieved through the competitive binding of PtdIns(3,4,5)P3 and Ca2+/CaM within its RGS domain. Competitive binding occurs exclusively within the RGS domain and involves a cluster of positively charged residues located on the surface opposite to the Ga interaction site. In the RGS proteins conserving these residues, the reciprocal regulation by PtdIns(3,4,5)P3 and Ca2+/CaM may be important for their physiological regulation of G-protein signalling.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.