白念珠菌钙稳态系统及钙信号途径的研究进展

白念珠菌是临床重要的条件致病菌,其胞内的钙稳态及钙信号途径与宿主侵染、压力应答等诸多生理过程紧密相关。研究该菌的钙稳态系统及钙信号调控网络,对明确白念珠菌的侵染机制与耐药机理,以及开发具有新靶点的抗真菌药物具有重要意义。本文对这些内容的研究进展进行了综述。     

Oxidative-induced membrane damage in diabetes lymphocytes: Effects on intracellular Ca2 + homeostasis

Oxidative stress is linked to several human diseases, including diabetes. However, the intracellular signal transduction pathways regulated by reactive oxygen species (ROS) remain to be established. Deleterious effects of ROS stem from interactions with various ion transport proteins such as ion channels and pumps, primarily altering Ca^{2 +} homeostasis and inducing cell dysfunction. This study characterized the Ca^{2 +} transport system in lymphocytes of patients with type-2 diabetes, evaluating the possible correlation between cell modifications and the existence of specific oxidative stress damage. Lymphocytes from type-2 diabetes patients displayed oxidative stress features (accumulation of some ROS species, membrane peroxidation, increase in protein carbonyls, increase in SOD and Catalase activity) and Ca^{2 +} dyshomeostasis (modified voltage-dependent and inositol 1,4,5-triphosphate-mediated Ca^{2 +} channel activities, decrease in Ca^{2 +} pumps activity). The data support a correlation between oxidative damage and alterations in intracellular Ca^{2 +} homeostasis, possibly due to modification of the ionic control in lymphocytes of type-2 diabetes patients.     

Calcium Signaling in Plant Endosymbiotic Organelles： Mechanism and Role in Physiology

Recent studies have demonstrated that chloroplasts and mitochondria evoke specific Ca2＋ signals in response to biotic and abiotic stresses in a stress-dependent manner. The identification of Ca2＋ transporters and Ca2＋signaling mol- ecules in chloroplasts and mitochondria implies that they play roles in controlling not only intra-organellar functions, but also extra-organellar processes such as plant immunity and stress responses. It appears that organellar Ca2＋ signaling might be more important to plant cell functions than previously thought. This review briefly summarizes what is known about the molecular basis of Ca2＋ signaling in plant mitochondria and chloroplasts.     

H2S与Ca^2＋协同增强谷子对Cr^6＋胁迫的耐受

继一氧化氮（NO）和一氧化碳（CO）之后,第三种气体信号分子硫化氢（H2S）对植物体生长发育和环境胁迫应答的调控正在受到越来越多的关注。钙离子（Ca2＋）是重要的第二信使,参与植物对多种胁迫的响应。该实验以谷子这种抗逆性较强的作物为材料,对其响应六价铬（Cr6＋）胁迫过程中H2S和Ca2＋45号的互作进行了研究。结果表明,Cr6＋胁迫显著激活谷子幼苗的H2s产生系统,外源H2S预处理能明显降低Cr6＋胁迫对谷子根尖细胞的损伤,而H2S的合成抑制剂羟胺（HA）预处理,使得Cr6＋对谷子的毒害增强;进一步实验发现,H2S能激活Ca2＋信号下游相关基因的表达,同时Ca＋能增强H2S的产生,表明在植物体内H2S和Ca＋信号存在复杂的联系。该研究也证明,H2S和ca2＋可以通过调节重金属离子转运蛋白增强谷子对Cr6＋的耐受。     

植物钙感受器及其介导的逆境信号途径

钙信号是植物生长发育和逆境响应的重要调控因子, 是植物生理与逆境生物学研究领域中的热点之一。当植物细胞受到外界逆境刺激时, 其胞内会产生具有时空特异性的Ca2+信号变化, 这种变化首先被胞内钙感受器所感知并解码, 再由钙感受器互作蛋白将信号传递到下游, 从而激活下游早期响应基因的表达或相关离子通道的活性, 最终产生特异性逆境响应。植物细胞通过感知胞内钙信号的变化如何识别来自外界不同性质或不同强度的刺激, 是近几年植物生物学家所关注的科学问题。文章主要总结了近几年在植物钙感受器研究领域中的最新进展, 包括钙依赖蛋白激酶(CDPKs)、钙调素(CaMs)、类钙调素蛋白(CMLs)、类钙调磷酸酶B蛋白(CBLs)及其互作蛋白激酶(CIPKs)等的结构、功能及其介导的逆境信号途径, 并提供新的见解和展望。     

钙指示剂的发展及其研究现状

钙指示剂常被用于细胞及细胞器钙信号的检测,是钙信号转导研究中必不可少的工具.目前的钙指示剂分两大类,包括化学钙指示剂,如Fura-2、Indo-1、Fluo-4等,和基因编码的钙指示蛋白如D1ER、GCaMP、CEPIAler等.随着技术的发展及研究需求的不断提升,各版本的钙指示剂也在不断更新.本文对已有的钙指示剂进行...     

Cellular calcium and redox regulation: the mediator of vertebrate environmental sex determination?

Many reptiles and some fish determine offspring sex by environmental cues such as incubation temperature. The mechanism by which environmental signals are captured and transduced into specific sexual phenotypes has remained unexplained for over 50 years. Indeed, environmental sex determination (ESD) has been viewed as an intractable problem because sex determination is influenced by a myriad of genes that may be subject to environmental influence. Recent demonstrations of ancient, conserved epigenetic processes in the regulatory response to environmental cues suggest that the mechanisms of ESD have a previously unsuspected level of commonality, but the proximal sensor of temperature that ultimately gives rise to one sexual phenotype or the other remains unidentified. Here, we propose that in ESD species, environmental cues are sensed by the cell through highly conserved ancestral elements of calcium and redox (CaRe) status, then transduced to activate ubiquitous signal transduction pathways, or influence epigenetic processes, ultimately to drive the differential expression of sex genes. The early evolutionary origins of CaRe regulation, and its essential role in eukaryotic cell function, gives CaRe a propensity to be independently recruited for diverse roles as a ‘cellular sensor’ of environmental conditions. Our synthesis provides the first cohesive mechanistic model connecting environmental signals and sex determination pathways in vertebrates, providing direction and a framework for developing targeted experimentation.     

Modeling the Calcium Signaling in Stomatal Guard Cells under the Action of Abscisic Acid

A theoretical model of calcium signaling is presented that simulates oscillations of cytoplasmic calcium concentration ([Ca²⁺]_cyt) in stomatal guard cells under the action of abscisic acid. The model is based on the kinetics of inositol 1,4,5-trisphosphate-sensitive calcium channels of endoplasmic reticulum and cyclic ADP-ribose-sensitive calcium channels of the tonoplast. The operation of two energy-dependent pumps—the Ca²⁺-ATPase of the endoplasmic reticulum and the Ca²⁺/H⁺ antiporter of the tonoplast—is also included in the model. It is shown that the removal of excessive Ca²⁺ from the cytoplasm by the tonoplast Ca²⁺/H⁺ antiporter is the main factor accounting for generation of [Ca²⁺]_cyt oscillations at a wide range of ABA concentrations (0.01–1 M). The long period of [Ca²⁺]_cyt oscillations in plant cells is explained by a slow release from inhibition of inositol 1,4,5-trisphosphate-gated calcium channels.     

Modulation of the voltage sensor of L-type Ca2+ channels by intracellular Ca2+

Both intracellular calcium and transmembrane voltage cause inactivation, or spontaneous closure, of L-type (CaV1.2) calcium channels. Here we show that long-lasting elevations of intracellular calcium to the concentrations that are expected to be near an open channel (>/=100 microM) completely and reversibly blocked calcium current through L-type channels. Although charge movements associated with the opening (ON) motion of the channel's voltage sensor were not altered by high calcium, the closing (OFF) transition was impeded. In two-pulse experiments, the blockade of calcium current and the reduction of gating charge movements available for the second pulse developed in parallel during calcium load. The effect depended steeply on voltage and occurred only after a third of the total gating charge had moved. Based on that, we conclude that the calcium binding site is located either in the channel's central cavity behind the voltage-dependent gate, or it is formed de novo during depolarization through voltage-dependent rearrangements just preceding the opening of the gate. The reduction of the OFF charge was due to the negative shift in the voltage dependence of charge movement, as previously observed for voltage-dependent inactivation. Elevation of intracellular calcium concentration from approximately 0.1 to 100-300 microM sped up the conversion of the gating charge into the negatively distributed mode 10-100-fold. Since the "IQ-AA" mutant with disabled calcium/calmodulin regulation of inactivation was affected by intracellular calcium similarly to the wild-type, calcium/calmodulin binding to the "IQ" motif apparently is not involved in the observed changes of voltage-dependent gating. Although calcium influx through the wild-type open channels does not cause a detectable negative shift in the voltage dependence of their charge movement, the shift was readily observable in the Delta1733 carboxyl terminus deletion mutant, which produces fewer nonconducting channels. We propose that the opening movement of the voltage sensor exposes a novel calcium binding site that mediates inactivation.     

钙信号在卵母细胞激活中的作用

钙信号是胞内主要的第二信使之一,发挥广泛的作用如细胞分裂、细胞凋亡等,对细胞的生命活动起着非常重要的作用。在精子和卵母细胞中,钙信号对精子获能、顶体反应、卵母细胞成熟、受精及卵裂等一系列复杂的过程有非常重要的影响。现就Ca2 在卵母细胞中的释放机制、信号转导途径、调控功能作一综述。     

Intracellular calcium signals and control of cell proliferation: how many mechanisms?

The progression through the cell cycle in non-transformed cells is under the strict control of extracellular signals called mitogens, that act by eliciting complex cascades of intracellular messengers. Among them, increases in cytosolic free calcium concentration have been long realized to play a crucial role; however, the mechanisms coupling membrane receptor activation to calcium signals are still only partially understood, as are the pathways of calcium entry in the cytosol. This article centers on the role of calcium influx from the extracellular medium in the control of proliferative processes, and reviews the current understanding of the pathways responsible for this influx and of the second messengers involved in their activation.