Neuroplastin: cell adhesion molecule and signaling receptor

Neuroplastin (Np) is a glycoprotein that belongs to the immunoglobulin superfamily of cell adhesion molecules. It exists in two isoforms, Np55 and Np65, named according to their apparent molecular weights. Neuroplastins were first identified as synapse-specific proteins, but subsequent findings have shown that Np65 is indeed expressed only in the brain, whereas Np55 is found in wide range of tissues. Since their discovery, the knowledge of Nps expanded, implicating them in various processes, including neuronal differentiation and synaptic plasticity. Here, we will review the Np structure and mechanisms involved in Np signaling and discuss the functions of Nps in the nervous system.     

Sucrose signaling in plants: A world yet to be explored

The role of sucrose as a signaling molecule in plants was originally proposed several decades ago. However, recognition of sucrose as a true signal has been largely debated and only recently this role has been fully accepted. The best-studied cases of sucrose signaling involve metabolic processes, such as the induction of fructan or anthocyanin synthesis, but a large volume of scattered information suggests that sucrose signals may control a vast array of developmental processes along the whole life cycle of the plant. Also, wide gaps exist in our current understanding of the intracellular steps that mediate sucrose action. Sucrose concentration in plant tissues tends to be directly related to light intensity, and inversely related to temperature, and accordingly, exogenous sucrose supply often mimics the effect of high light and cold. However, many exceptions to this rule seem to occur due to interactions with other signaling pathways. In conclusion, the sucrose role as a signal molecule in plants is starting to be unveiled and much research is still needed to have a complete map of its significance in plant function.     

'Srcasm: a novel Src activating and signaling molecule.

The Src family tyrosine kinase, Fyn, can facilitate regulation of cell proliferation and differentiation. Mice with mutations in the fyn gene have defects in the brain, immune system, and epidermal differentiation. To identify molecules that may interact with Fyn in the epidermis, we performed a yeast two-hybrid interaction screen of a murine keratinocyte library. A novel adaptor-like molecule was isolated and termed Srcasm for Src activating and signaling molecule. Murine Srcasm is a 52.7-kDa protein that contains a VHS membrane association domain and a number of tyrosine motifs suggesting that it may be a substrate for Src family kinases and serve as an adaptor protein. Northern blot analysis of murine tissues demonstrates that Srcasm expression is highest in brain and kidney. In situ hybridization analysis reveals that srcasm mRNA is expressed in regions of the epidermis and hair follicle where keratinocyte differentiation occurs. In the brain, srcasm mRNA distribution correlates with that of fyn, with both being highly expressed in the hippocampal and cerebellar Purkinje neurons. Fyn can phosphorylate Srcasm, and association of these molecules relies on cooperative binding between the SH2 and SH3 domains of Fyn and corresponding canonical binding sites in Srcasm. Srcasm is capable of interacting with Grb2 and the regulatory subunit of phosphoinositide 3-kinase, p85, in a phosphorylation-dependent manner. The evidence suggests that Srcasm may help promote Src family kinase signaling in cells.     

Subcellular Metabolite Levels in Spinach Leaves : Regulation of Sucrose Synthesis during Diurnal Alterations in Photosynthetic Partitioning

The alterations of subcellular metabolite levels during the day in spinach leaves have been investigated using nonaqueous density gradient centrifugation to separate chloroplasts, cytosol, and vacuole. The results provide direct evidence for the role of sucrose phosphate synthase and cytosolic fructose 1,6-bisphosphatase in regulating sucrose synthesis in leaves and also show that the phosphate translocator is kinetically limiting in vivo.     

Sucrose control of phytochrome A signaling in Arabidopsis.

The expression of the Arabidopsis plastocyanin (PC) gene is developmentally controlled and regulated by light. During seedling development, PC gene expression is transiently induced, and this induction can be repressed by sucrose. In transgenic seedlings carrying a PC promoter-luciferase fusion gene, the luciferase-induced in vivo luminescence was similarly repressed by sucrose. From a mutagenized population of such transgenic seedlings, we selected for mutant seedlings that displayed a high luminescence level when grown on a medium with 3% sucrose. This screening of mutants resulted in the isolation of several sucrose-uncoupled (sun) mutants showing reduced repression of luminescence by sucrose. Analysis of the sun mutants revealed that the accumulation of PC and chlorophyll a/b binding protein (CAB) mRNA was also sucrose uncoupled, although the extent of uncoupling varied. The effect of sucrose on far-red light high-irradiance responses was studied in wild-type, sun1, sun6, and sun7 seedlings. In wild-type seedlings, sucrose repressed the far-red light-induced cotyledon opening and inhibition of hypocotyl elongation. sun7 seedlings showed reduced repression of these responses. Sucrose also repressed the far-red light-induced block of greening in wild-type seedlings, and both sun6 and sun7 were affected in this response. The results provide evidence for a close interaction between sucrose and light signaling pathways. Moreover, the sun6 and sun7 mutants genetically identify separate branches of phytochrome A-dependent signal transduction pathways.     

Glutathione as a signaling molecule: Another challenge to pathogens

Plants harbor a variety of signaling molecules which are members of a vast array of signaling networks in maintaining their physiological balance. The well known members up till now are salicylic acid (SA), jasmonic acid (JA), ethylene (ET), abscissic acid (ABA) and reactive oxygen species (ROS) which are employed by plants for their adaptation to various environmental stresses in order to survive. GSH is gradually gaining importance and becoming a molecule of interest to a number of researchers especially in relation to plant defense to pathogens. Although the role of GSH in plant defense has long been known, a dearth of information still exists regarding the mechanism underlying this defense response. This review highlights on the progress made in the cross-communication of GSH with other established signaling molecules through which GSH acts in abating biotic stress.Key words: glutathione, salicylic acid, biotrophic pathogen, NPR1, crosstalk, signalingGlutathione, popularly known as the “master anioxidant” or “super defender,” is a nearly ubiquitous non-protein tripeptide thiol compound found in both prokaryotes and eukaryotes^1–3 except for some organisms which use different other thiol cofactors. This molecule helps to prevent or even reduce the effect of certain human diseases which are of major concern in today''s world including cancer, inflammation, kwashiorkor, Alzheimer''s disease, Parkinson''s disease, sickle cell anaemia, liver disease, cystic fibrosis, HIV, AIDS, infection, heart attack, stroke and diabetes. GSH, in animals, participates in the detoxification of ROS and xenobiotics, plays a major role in cell proliferation and death, DNA synthesis and repair, regulation of protein synthesis, prostaglandin synthesis, amino acid transport and enzyme activation, maintains essential thiol status, regulates immune functions, plays a role in spermatogenesis and sperm maturation and so on. In prokaryotes, GSH is one of the most abundant thiols as well and is present in cyanobacteria and proteobacteria. In bacteria, in addition to its key role in maintaining the proper oxidation state of protein thiols, GSH also serves a key function in protecting the cell from the action of low pH, chlorine compounds and oxidative as well as osmotic stresses.The well known functions performed by this molecule in plants are as a major player in redox chemistry, heavy metals and electrophilic xenobiotics elimination, serving as electron donor for biochemical reactions, long-distance transport of reduced sulfur, stress defense gene expression, posttranslational modifications through glutathionylation, role in biotic and abiotic stresses and so on.^4–13 Over the past three decades, GSH has been known to be involved in defense reactions against a variety of pathogens in addition to the induction of various defense genes. GSH when supplied at various concentrations to the cell suspension culture of bean induced several genes encoding enzymes that participate in the biosynthesis of lignin and phytoalexins.¹⁴ Early reports also found that GSH supplementation partly mimicked induction of chalcone synthase, the expression of which occurs as a result of fungal elicitor stimulation in soybean.¹⁵ Bean and soybean cells treated with fungal elicitor or GSH causes the rapid insolubilization of hydroxy-proline-rich structural proteins in the cell wall.¹⁶ Previous report also revealed that significant increase in GSH levels occurred as a result of enhanced resistance of melon and tomato roots against Fusarium oxysporum brought about by herbicides.¹⁷ In compatible barley-barley powdery mildew interactions the ascorbate-GSH cycle and other antioxidative enzymes (e.g., glutathione S-transferase) are activated and these processes might diminish the damaging effects of oxidative stress. However, in incompatible interactions these antioxidative reactions are not or are only slightly activated.¹⁸ A considerable accumulation of GSH and, in particular, oxidized glutathione (GSSG) has been observed in tomato cells carrying Cf-9 or Cf-2 resistance genes after treatment with race-specific elicitors of the fungus Cladosporium fulvum.¹⁹ Ball et al. reported that 32 stress-responsive genes were altered due to changed GSH metabolism in Arabidopsis rax1-1 and cad2-1, mutants of γ-ECS. Previous studies also reported that Arabidopsis pad2-1 mutant with only 22% of wild-type amounts of GSH were susceptible to Pseudomonas syringae as well as Phytophthora brassicae.^20–22 Additionally, according to a recent report, enhanced resistance of transgenic tobacco with enhanced level of GSH was observed against P. syringae.²³Recent reports have found the role of GSH in cell signaling and in signaling pathways induced by different phytohormones. This review was an effort to throw some light on understanding the role of GSH as a signaling molecule by discussing the interrelationship of this multi-faceted molecule with other established signaling molecules which have well documented signaling roles in plants against biotic and abiotic stresses.     

Lipid peroxidation and cell cycle signaling: 4-hydroxynonenal,a key molecule in stress mediated signaling

Role of lipid peroxidation products, particularly 4-hydroxynonenal (4-HNE) in cell cycle signaling is becoming increasingly clear. In this article, recent studies suggesting an important role of 4-HNE in stress mediated signaling for apoptosis are critically evaluated. Evidence demonstrating the modulation of UV, oxidative stress, and chemical stress mediated apoptosis by blocking lipid peroxidation by the alpha-class glutathione S-transferases (GSTs) is presented which suggest an important role of these enzymes in protection against oxidative stress and a role of lipid peroxidation products in stress mediated signaling. Overexpression of 4-HNE metabolizing GSTs (mGSTA4-4, hGSTA4-4, or hGST5.8) protects cells against 4-HNE, oxidative stress (H(2)O(2) or xanthine/xanthine oxidase), and UV-A mediated apoptosis by blocking JNK and caspase activation suggesting a role of 4-HNE in the mechanisms of apoptosis caused by these stress factors. The intracellular concentration of 4-HNE appears to be crucial for the nature of cell cycle signaling and may be a determinant for the signaling for differentiation, proliferation, transformation, or apoptosis. The intracellular concentrations of 4-HNE are regulated through a coordinated action of GSTs (GSTA4-4 and hGST5.8) which conjugate 4-HNE to GSH to form the conjugate (GS-HNE) and the transporter 76 kDa Ral-binding GTPase activating protein (RLIP76), which catalyze ATP-dependent transport of GS-HNE. A mild stress caused by heat, UV-A, or H(2)O(2)with no apparent effect on the cells in culture causes a rapid, transient induction of hGST5.8 and RLIP76. These stress preconditioned cells acquire ability to metabolize and exclude 4-HNE at an accelerated pace and acquire relative resistance to apoptosis by UV and oxidative stress as compared to unconditioned control cells. This resistance of stress preconditioned cells can be abrogated by coating the cells with anti-RLIP76 antibodies which block the transport of GS-HNE. These studies and previous reports discussed in this article strongly suggest a key role of 4-HNE in stress mediated signaling.     

脂质活性信号分子鞘氨醇-1-磷酸及其生物学特性

鞘氨醇-1-磷酸(sphingosine-1-phosphate,S1P)是目前颇受关注的脂质信号分子.体内S1P主要由红细胞内鞘氨醇激酶催化鞘氨醇合成,后经由ATP结合盒式转运子释放入血浆.血浆S1P超过半数存在于高密度脂蛋白和血清白蛋白上.S1P可通过直接胞内作用和激活其特异性G蛋白偶联受体产生多种重要生物学效应.S1P1-5型受体在体内各类型组织和细胞表达水平不同,参与包括细胞增殖、存活、迁移等多种生物学过程.     

Sucrose triggers a novel signaling cascade promoting Bacillus subtilis rhizosphere colonization

Beneficial rhizobacteria promote plant growth and protect plants against phytopathogens. Effective colonization on plant roots is critical for the rhizobacteria to exert beneficial activities. How bacteria migrate swiftly in the soil of semisolid or solid nature remains unclear. Here we report that sucrose, a disaccharide ubiquitously deployed by photosynthetic plants for fixed carbon transport and storage, and abundantly secreted from plant roots, promotes solid surface motility (SSM) and root colonization by Bacillus subtilis through a previously uncharacterized mechanism. Sucrose induces robust SSM by triggering a signaling cascade, first through extracellular synthesis of polymeric levan, which in turn stimulates strong production of surfactin and hyper-flagellation of the cells. B. subtilis poorly colonizes the roots of Arabidopsis thaliana mutants deficient in root-exudation of sucrose, while exogenously added sucrose selectively shapes the rhizomicrobiome associated with the tomato plant roots, promoting specifically bacilli and pseudomonad. We propose that sucrose activates a signaling cascade to trigger SSM and promote rhizosphere colonization by B. subtilis. Our findings also suggest a practicable approach to boost prevalence of beneficial Bacillus species in plant protection.Subject terms: Soil microbiology, Bacteriology     

Activated leukocyte cell adhesion molecule modulates neurotrophin signaling

Cell adhesion molecules of the immunoglobulin superfamily (IgCAMs) have been shown to modulate growth factor signaling and follow complex trafficking pathways in neurons. Similarly, several growth factors, including members of the neurotrophin family, undergo axonal retrograde transport that is required to elicit their full signaling potential in neurons. We sought to determine whether IgCAMs that enter the axonal retrograde transport route co-operate with neurotrophin signaling. We identified activated leukocyte cell adhesion molecule (ALCAM), a protein involved in axon pathfinding and development of the neuromuscular junction, to be associated with an axonal endocytic compartment that contains neurotrophins and their receptors. Although ALCAM enters carriers that are transported bidirectionally in motor neuron axons, it is predominantly co-transported with the neurotrophin receptor p75(NTR) toward the cell body. ALCAM was found to specifically potentiate nerve growth factor (NGF)-induced differentiation and signaling. The extracellular domain of ALCAM is both necessary and sufficient to potentiate NGF-induced neurite outgrowth, and its homodimerization is required for this novel role. Our findings indicate that ALCAM synergizes with NGF to induce neuronal differentiation, raising the possibility that it functions not only as an adhesion molecule but also in the modulation of growth factor signaling in the nervous system.     

无机盐和蔗糖浓度对白色紫锥菊不定根生长及次生代谢产物积累影响

利用组织培养技术结合高效液相色谱法,考察了液体悬浮培养中无机盐和蔗糖浓度对白色紫锥菊不定根生长以及紫锥菊苷、菊苣酸、氯原酸和酚类化合物积累的影响.结果表明:白色紫锥菊不定根在高或低浓度无机盐和蔗糖培养基中的生长及次生代谢产物含量均较低,不定根生长最适培养基为0.75 MS +5％蔗糖,培养30 d后不定根中紫锥菊苷含量为7.40 mg/g DW,菊苣酸为3.96 mg/g DW,氯原酸含量达3.79 mg/g DW,总酚含量达25.62 mg/g DW.本研究为进一步大规模培养富含紫锥菊苷、菊苣酸的白色紫锥菊不定根奠定了理论和实践基础.     

New costimulatory families: signaling lymphocytic activation molecule in adaptive allergic responses

The generation of an allergic immune response requires at least two signals for complete activation of T cells. Costimulatory molecules are integral to the second signal. In this review, we analyze the costimulatory molecule signaling lymphocytic activation molecule (SLAM) and other recently described SLAM family members. We highlight recent findings that position SLAM as critical for allergic inflammation and its role in modulation of cytokine secretion. Furthermore, a possible role of SLAM as a link between the adaptive and innate immune response is also discussed. Understanding the role of costimulatory molecules, including SLAM and SLAM family members, may elucidate mechanisms involved in the allergic immune response, and suggest potential therapeutic opportunities.     

Diurnal Changes in Maize Leaf Photosynthesis : II. Levels of Metabolic Intermediates of Sucrose Synthesis and the Regulatory Metabolite Fructose 2,6-Bisphosphate

Diurnal changes in the regulatory metabolite, fructose-2,6-bisphosphate (F26BP), and key metabolic intermediates of sucrose biosynthesis were studied in maize (Zea mays L. cv Pioneer 3184) during a day-night cycle. Whole leaf concentrations of dihydroxyacetonephosphate (DHAP) and fructose 1,6-bisphosphate changed markedly during the photoperiod. DHAP concentration was correlated positively with the rate of sucrose formation in vivo (assimilate export plus sucrose accumulation) and extractable activity of sucrose phosphate synthase (SPS). The changes closely followed net photosynthetic rate, which tracked irradiance. The other metabolic intermediates measured (glucose 6-phosphate, fructose 6-phosphate, and UDP-glucose) were either relatively constant over the 24 hour period or changed in a different pattern. Diurnal changes in leaf F26BP concentrations were pronounced, and fundamentally different than the pattern reported with other species. F26BP concentration decreased at the beginning of the day and remained low and constant; a 3- to 4-fold increase occurred with darkness, and slowly declined thereafter. In general, leaf F26BP concentration was negatively correlated with net photosynthetic rate, and also leaf DHAP concentration. Consequently, co-ordination of the regulation of cytosolic fructose 1,6-bisphosphatase and SPS was apparent. The results support the postulate that in maize leaves the activation state of SPS may be dependent on availability of DHAP and possibly other metabolites.     

Inhibition of Sucrose:Sucrose Fructosyl Transferase by Cations and Ionic Strength

Fructans are storage carbohydrates found in many temperate grasses. The first enzyme in the biosynthetic pathway of most fructans is sucrose:sucrose fructosyl transferase (SST). In this report, we demonstrate that K+ and ionic strength noncompetitively inhibit the activity of SST from wheat (Triticum aestivum L.) stems. The Ki for this inhibition is high, 122 mM, but in the range of concentrations of K+ found in the tissue (205-314 mM). Addition of KCl to the assay system had no effect on the pH optimum (5.5) or the Km for sucrose (266 mM) but reduced the Vmax. At equivalent ionic strengths, inhibition by choline chloride was about half that of KCl, indicating that inhibition by ionic strength might be responsible for approximately 50% of the KCl inhibition. Inhibition by LiCl and (NH4)2SO4 was similar to that by choline chloride. Soluble invertase activity found in the SST preparations was less sensitive to KCl and more sensitive to choline chloride than was SST. SST from barley (Hordeum vulgare L.) stems and leaves, as well as SST from leaves of orchardgrass (Dactylis glomerata), was also inhibited by KCl. SST from onion (Allium cepa L.) bulbs and asparagus (Asparagus officinalis L.) stems was not inhibited by KCl; thus, inhibition of activity by KCl is not a universal characteristic of SST from all sources.