Does efficiency sensing unify diffusion and quorum sensing?

Quorum sensing faces evolutionary problems from non-producing or over-producing cheaters. Such problems are circumvented in diffusion sensing, an alternative explanation for quorum sensing. However, both explanations face the problems of signalling in complex environments such as the rhizosphere where, for example, the spatial distribution of cells can be more important for sensing than cell density, which we show by mathematical modelling. We argue that these conflicting concepts can be unified by a new hypothesis, efficiency sensing, and that some of the problems associated with signalling in complex environments, as well as the problem of maintaining honesty in signalling, can be avoided when the signalling cells grow in microcolonies.     

The calcium sensing receptor: from calcium sensing to signaling

The Ca2+-sensing receptor(the Ca SR),a G-protein-coupled receptor,regulates Ca2+ homeostasis in the body by monitoring extracellular levels of Ca2+([Ca2+]o) and responding to a diverse array of stimuli.Mutations in the Ca2+-sensing receptor result in hypercalcemic or hypocalcemic disorders,such as familial hypocalciuric hypercalcemia,neonatal severe primary hyperparathyroidism,and autosomal dominant hypocalcemic hypercalciuria.Compelling evidence suggests that the Ca SR plays multiple roles extending well beyond not only regulating the level of extracellular Ca2+ in the human body,but also controlling a diverse range of biological processes.In this review,we focus on the structural biology of the Ca SR,the ligand interaction sites as well as their relevance to the disease associated mutations.This systematic summary will provide a comprehensive exploration of how the Ca SR integrates extracellular Ca2+ into intracellular Ca2+ signaling.     

细菌的群体行为调控机制-Quorum sensing

群体效应(Quorum sensing)是近来日益受到广泛关注的一种细菌群体行为调控机制,很多细菌有这种能力,即分泌一种或多种自诱导剂(Autoinducer),细菌通过感应这些自诱导剂来判断菌群密度和周围环境变化,当菌群数达到一定的阀值(quorum,菌落或集落数)后,启动相应一系列基因的调节表达,以调节菌体的群体行为。不同类型的细菌具有不同的群体效应调节系统,很多细菌分泌同一种诱导剂,以此调控不同种类细菌间的作用行为。群体效应系统在自诱导剂与受体之间存在专一性,同时又在调节基因和信号传递系统中体现出多样性和复杂性。由于不少人或植物的病原菌的致病机制等受群体效应的调控,该机制已成为医学等领域的研究热点。     

假单胞菌Quorum sensing调控体系

群体感应(Quorum sensing,QS)是近来受到广泛关注的一种细菌群体行为调控机制,通过感应一些信号分子如酰基高丝氨酸环内酯(acyl-homoserine lactone,AHL)来判断菌群密度和周围环境变化,假单胞菌中同样也有AHL信号分子,当信号达到一定的浓度阈值时,能启动菌体中相关基因的表达来适应环境中的变化,从而调节菌体的群体行为(如致病性及群体生长调节)。众多报道说明了假单胞菌的群体感应调节系统是由一些全面的调节子所调控的。本文系统介绍了假单胞菌群体感应调控系统,并分析假单胞菌在该系统中复杂的应答反应。     

L-histidine sensing by calcium sensing receptor inhibits voltage-dependent calcium channel activity and insulin secretion in β-cells

AimsOur goal was to test the hypothesis that the histidine-induced activation of calcium sensing receptor (CaR) can regulate calcium channel activity of L-type voltage dependent calcium channel (VDCC) due to increased spatial interaction between CaR and VDCC in β-cells and thus modulate glucose-induced insulin secretion.Main methodsRat insulinoma (RINr1046-38) insulin-producing β-cells were cultured in RPMI-1640 medium on 25 mm diameter glass coverslips in six-well culture plates in a 5% CO₂ incubator at 37 °C. The intracellular calcium concentration, [Ca²⁺]_i, was determined by ratio fluorescence microscopy using Fura-2AM. The spatial interactions between CaR and L-type VDCC in β-cells were measured by immunofluorescence confocal microscopy using a Nikon C1 laser scanning confocal microscope. The insulin release was determined by enzyme-linked immunosorbent assay (ELISA).Key findingsThe addition of increasing concentrations of L-histidine along with 10 mM glucose resulted in 57% decrease in [Ca²⁺]_i. The confocal fluorescence imaging data showed 5.59 to 8.62-fold increase in colocalization correlation coefficient between CaR and VDCC in β-cells exposed to L-histidine thereby indicating increased membrane delimited spatial interactions between these two membrane proteins. The insulin ELISA data showed 54% decrease in the 1st phase of glucose-induced insulin secretion in β-cells exposed to increasing concentrations of L-histidine.SignificanceL-histidine-induced increased spatial interaction of CaR with VDCC can inhibit calcium channel activity of VDCC and consequently regulate glucose-induced insulin secretion by β-cells. The L-type VDCC could therefore be a potential therapeutic target in diabetes.     

Acclimation to Soil Flooding–sensing and signal-transduction

Flooding results in major changes in the soil environment. The slow diffusion rate of gases in water limits the oxygen supply, which affects aerobic root respiration as well as many (bio)geochemical processes in the soil. Plants from habitats subject to flooding have developed several ways to acclimate to these growth-inhibiting conditions, ranging from pathways that enable anaerobic metabolism to specific morphological and anatomical structures that prevent oxygen shortage. In order to acclimate in a timely manner, it is crucial that a flooding event is accurately sensed by the plant. Sensing may largely occur in two ways: by the decrease of oxygen concentration, and by an increase in ethylene. Although ethylene sensing is now well understood, progress in unraveling the sensing of oxygen has been made only recently. With respect to the signal-transduction pathways, two types of acclimation have received most attention. Aerenchyma formation, to promote gas diffusion through the roots, seems largely under control of ethylene, whereas adventitious root development appears to be induced by an interaction between ethylene and auxin. Parts of these pathways have been described for a range of species, but a complete overview is not yet available. The use of molecular-genetic approaches may fill the gaps in our knowledge, but a lack of suitable model species may hamper further progress.     

O2 sensing: only skin deep?

In this issue, two papers implicate histone H3 lysine 56 acetylation in histone deposition in chromatin. Li et al. (2008) show that acetylation of H3K56 promotes S phase chromatin assembly that is mediated by the histone chaperones CAF-1 and Rtt106. Chen et al. (2008) establish that the acetylation mark promotes chromatin reassembly following DNA double-strand break repair.     

Cellulose-binding domains: cellulose associated-defensive sensing partners?

The cellulose-binding domains (CBDs) in the Phytophthora cellulose-binding elicitor lectin (CBEL) are potent elicitors of plant defence responses. Induction of defence has also been reported in various cellulose-deficient mutants of Arabidopsis thaliana. Based on these observations, we propose a model linking cellulose alteration to defence induction. This integrates the fast increase in cytosolic calcium recorded in response to CBEL, mechano-stimulated calcium uptake mechanisms, and proteins that interact functionally with the cellulose synthase complex. In this context, CBDs emerge as new tools to decipher the signalling cascades that result from cell wall-cellulose perturbations.     

Uncovering directional sensing: where are we headed?

We survey aspects of directional sensing, i.e. how a cell interprets differences in the external concentration of a chemoattractant to guide its motion, from the perspective of systems biology. We focus on questions that need to be addressed using a combination of modelling and experimental approaches. After briefly summarising the ideas underlying recent modelling efforts, we discuss a variety of experimental questions which are motivated by these models. Some of these questions focus on basic features of the chemotactic response, without involving much biochemistry, while others focus on filling some of the gaps in the biochemistry, which have been brought to light by the models. The emphasis is on systematic quantitative experiments that will unambiguously resolve many of these issues. Finally, we describe some current challenges for theoretical modelling and survey some of the theoretical tools and approaches employed to model the chemotaxis pathways.     

Neuronal glucose sensing: still a physiological orphan?

Although hypothalamic glucose sensing is a long-established phenomenon, its physiological role remains unclear. New studies (Parton et al., 2007; Claret et al., 2007) disrupting glucose sensing in pro-opiomelanocortin neurons via differing methods have yielded disparate energy and glucose homeostasis phenotypes, suggesting that neuronal glucose sensing is not critical for these processes.     

Distinct amino acid–sensing mTOR pathways regulate skeletal myogenesis

Signaling through the mammalian target of rapamycin (mTOR) in response to amino acid availability controls many cellular and developmental processes. mTOR is a master regulator of myogenic differentiation, but the pathways mediating amino acid signals in this process are not known. Here we examine the Rag GTPases and the class III phosphoinositide 3-kinase (PI3K) Vps34, two mediators of amino acid signals upstream of mTOR complex 1 (mTORC1) in cell growth regulation, for their potential involvement in myogenesis. We find that, although both Rag and Vps34 mediate amino acid activation of mTORC1 in C2C12 myoblasts, they have opposing functions in myogenic differentiation. Knockdown of RagA/B enhances, whereas overexpression of active RagB/C mutants impairs, differentiation, and this inhibitory function of Rag is mediated by mTORC1 suppression of the IRS1-PI3K-Akt pathway. On the other hand, Vps34 is required for myogenic differentiation. Amino acids activate a Vps34-phospholipase D1 (PLD1) pathway that controls the production of insulin-like growth factor II, an autocrine inducer of differentiation, through the Igf2 muscle enhancer. The product of PLD, phosphatidic acid, activates the enhancer in a rapamycin-sensitive but mTOR kinase–independent manner. Our results uncover amino acid–sensing mechanisms controlling the homeostasis of myogenesis and underline the versatility and context dependence of mTOR signaling.     

Sugar sensing and α-amylase gene repression in rice embryos

We used a transient expression system to study the mechanism by which carbohydrates repress a rice (Oryza sativa L.) α-amylase (EC 3.2.1.1) gene. Exogenously fed metabolizable carbohydrates are able to elicit repression of the α-amylase gene RAmy3D in the rice embryo, and our results indicate that repression is also triggered efficiently by endogenous carbohydrates. Glucose analogs that are taken up by plant cells but not phosphorylated by hexokinase are unable to repress the α-amylase gene studied, while 2-deoxyglucose, which is phosphorylable but not further metabolized, down-regulates RAmy3D promoter activity, indicating a role for hexokinase in the sugar-sensing mechanism triggering repression of the RAmy3D gene. We tested two different hexokinase inhibitors, mannoheptulose and glucosamine, but only the latter was able to relieve RAmy3D promoter activity from repression by endogenous carbohydrates. This correlates with the higher ability of glucosamine to inhibit the activity of rice hexokinases in vitro. The glucosamine-mediated relief of RAmy3D promoter activity from repression by endogenous carbohydrates does not correlate with a reduced rate of carbohydrate utilization. Received: 22 April 1997 / Accepted: 9 September 1997     

Do plants dynamically regulate nectar features through sugar sensing?

Nectar properties (volume, concentration, viscosity) change dynamically in time. As stated by Pedersen some decades ago (1958), “Nectar is not a static product remaining outside the plant once produced but is in close contact with the plant system.”¹ It is now evident that secretion may occur concomitantly with resorption and that the latter process sometimes continues after secretion has ended. The rate of the two processes may be modified dynamically by the plant in response to ecological and physiological constraints, maintaining a relatively constant nectar concentration to ensure pollinator visits (nectar homeostasis) and reallocating resources, especially during development of the ovules and pericarp after fertilization. We suspect that nectar resorption is under-estimated as a phenomenon, because it requires detailed information on the dynamics of nectar production throughout the life of the flower that is seldom available or taken into consideration. The cytological and molecular mechanisms involved in nectar resorption are almost completely unknown. Sugar sensing may have a fundamental role in nectar resorption and homeostasis. Due to direct contact with sugar solutions, nectaries may offer wide scope for insights into this phenomenon which has attracted interest as part of plant signalling systems.Key words: nectaries, nectar resorption, nectar homeostasis, nectar composition     

Adenosine A₂a receptors and O₂ sensing in development

Reduced mitochondrial oxidative phosphorylation, via activation of adenylate kinase and the resulting exponential rise in the cellular AMP/ATP ratio, appears to be a critical factor underlying O? sensing in many chemoreceptive tissues in mammals. The elevated AMP/ATP ratio, in turn, activates key enzymes that are involved in physiologic adjustments that tend to balance ATP supply and demand. An example is the conversion of AMP to adenosine via 5'-nucleotidase and the resulting activation of adenosine A(?A) receptors, which are involved in acute oxygen sensing by both carotid bodies and the brain. In fetal sheep, A(?A) receptors associated with carotid bodies trigger hypoxic cardiovascular chemoreflexes, while central A(?A) receptors mediate hypoxic inhibition of breathing and rapid eye movements. A(?A) receptors are also involved in hypoxic regulation of fetal endocrine systems, metabolism, and vascular tone. In developing lambs, A(?A) receptors play virtually no role in O? sensing by the carotid bodies, but brain A(?A) receptors remain critically involved in the roll-off ventilatory response to hypoxia. In adult mammals, A(?A) receptors have been implicated in O? sensing by carotid glomus cells, while central A(?A) receptors likely blunt hypoxic hyperventilation. In conclusion, A(?A) receptors are crucially involved in the transduction mechanisms of O? sensing in fetal carotid bodies and brains. Postnatally, central A(?A) receptors remain key mediators of hypoxic respiratory depression, but they are less critical for O? sensing in carotid chemoreceptors, particularly in developing lambs.     

Amino acid sensing mechanisms: an Achilles heel in cancer?

The act of increasing mass, either in non-dividing cells or in dividing cells seeking to provide new material for daughter cells, depends upon the continued presence of extracellular nutrients in order to conserve mass. For amino acid nutrients, it appears that their insufficiency for new protein synthesis is actively monitored by both prokaryotic and eukaryotic cells, eliciting appropriate cellular responses that may depend not only on bulk nutrient supply, but also on the abundance of specific amino acids.     

Does a quorum sensing mechanism direct the behavior of immune cells?

Quorum sensing is a decision-making process used by decentralized groups such as colonies of bacteria to trigger a coordinated behavior. The existence of decentralized coordinated behavior has also been suggested in the immune system. In this paper, we explore the possibility for quorum sensing mechanisms in the immune response. Cytokines are good candidates as inducer of quorum sensing effects on migration, proliferation and differentiation of immune cells. The existence of a quorum sensing mechanism should be explored experimentally. It may provide new perspectives into immune responses and could lead to new therapeutic strategies.     

Carboxymethylcellulose–gelatin–superoxidase dismutase electrode for amperometric superoxide radical sensing

A novel, highly sensitive superoxide dismutase biosensor for the direct and simultaneous determination of superoxide radicals was developed by immobilization of superoxide dismutase within carboxymethylcellulose-gelatin on a Pt electrode surface. The parameters affecting the performance of the biosensor were investigated. The response of the CMC-G-SOD biosensor was proportional to O (2) (·-) concentration and the detection limit was 1.25 × 10(-3) mM with a correlation coefficient of 0.9994. The developed biosensor exhibited high analytical performance with wider linear range, high sensitivity and low response time. The biosensor retained 89.8% of its sensitivity after use for 80 days. The support system enhanced the immobilization of superoxide dismutase and promoted the electron transfer of superoxide dismutase minimizing its fouling effect. The biosensor was quite effective not only in detecting O (2) (·-) , but also in determining the antioxidant properties of acetylsalicylic acid-based drugs and the anti-radical activity of healthy and cancerous human brain tissues.     

Gut sensing of dietary K⁺ intake increases renal K⁺excretion

Dietary K(+) intake may increase renal K(+) excretion via increasing plasma [K(+)] and/or activating a mechanism independent of plasma [K(+)]. We evaluated these mechanisms during normal dietary K(+) intake. After an overnight fast, [K(+)] and renal K(+) excretion were measured in rats fed either 0% K(+) or the normal 1% K(+) diet. In a third group, rats were fed with the 0% K(+) diet, and KCl was infused to match plasma [K(+)] profile to that of the 1% K(+) diet group. The 1% K(+) feeding significantly increased renal K(+) excretion, associated with slight increases in plasma [K(+)], whereas the 0% K(+) diet decreased K(+) excretion, associated with decreases in plasma [K(+)]. In the KCl-infused 0% K(+) diet group, renal K(+) excretion was significantly less than that of the 1% K(+) group, despite matched plasma [K(+)] profiles. We also examined whether dietary K(+) alters plasma profiles of gut peptides, such as guanylin, uroguanylin, glucagon-like peptide 1, and glucose-dependent insulinotropic polypeptide, pituitary peptides, such as AVP, α-MSH, and γ-MSH, or aldosterone. Our data do not support a role for these hormones in the stimulation of renal K(+) excretion during normal K(+) intake. In conclusion, postprandial increases in renal K(+) excretion cannot be fully accounted for by changes in plasma [K(+)] and that gut sensing of dietary K(+) is an important component of the regulation of renal K(+) excretion. Our studies on gut and pituitary peptide hormones suggest that there may be previously unknown humoral factors that stimulate renal K(+) excretion during dietary K(+) intake.