Developmental Regulation and Spatiotemporal Redistribution of the Sumoylation Machinery in the Rat Central Nervous System

International audienceBACKGROUND: Small Ubiquitin-like MOdifier protein (SUMO) is a key regulator of nuclear functions but little is known regarding the role of the post-translational modification sumoylation outside of the nucleus, particularly in the Central Nervous System (CNS). METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that the expression levels of SUMO-modified substrates as well as the components of the sumoylation machinery are temporally and spatially regulated in the developing rat brain. Interestingly, while the overall sumoylation is decreasing during brain development, there are progressively more SUMO substrates localized at synapses. This increase is correlated with a differential redistribution of the sumoylation machinery into dendritic spines during neuronal maturation. CONCLUSIONS/SIGNIFICANCE: Overall, our data clearly demonstrate that the sumoylation process is developmentally regulated in the brain with high levels of nuclear sumoylation early in the development suggesting a role for this post-translational modification during the synaptogenesis period and a redistribution of the SUMO system towards dendritic spines at a later developmental stage to modulate synaptic protein function

TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export

The metazoan TREX complex is recruited to mRNA during nuclear RNA processing and functions in exporting mRNA to the cytoplasm. Nxf1 is an mRNA export receptor, which binds processed mRNA and transports it through the nuclear pore complex. At present, the relationship between TREX and Nxf1 is not understood. Here we show that Nxf1 uses an intramolecular interaction to inhibit its own RNA-binding activity. When the TREX subunits Aly and Thoc5 make contact with Nxf1, Nxf1 is driven into an open conformation, exposing its RNA-binding domain, allowing RNA binding. Moreover, the combined knockdown of Aly and Thoc5 markedly reduces the amount of Nxf1 bound to mRNA in vivo and also causes a severe mRNA export block. Together, our data indicate that TREX provides a license for mRNA export by driving Nxf1 into a conformation capable of binding mRNA

Light-absorption spectroscopy of mutagen-DNA complex in presence of competing biologically active compounds

Abstract Mathematical analysis of absorption spectra of biologically active substances is presented. Two models of interactions of mutagen and caffeine with DNA analyzed and obtained binding parameters show good coincidence. Using different models, which take into account formation of various complexes, it is possible to calculate different binding parameters of such triple systems and choose the model describing corresponding system in the best way

Nxt1 Is Necessary for the Terminal Step of Crm1-Mediated Nuclear Export

Soluble factors are required to mediate nuclear export of protein and RNA through the nuclear pore complex (NPC). These soluble factors include receptors that bind directly to the transport substrate and regulators that determine the assembly state of receptor–substrate complexes. We recently reported the identification of NXT1, an NTF2-related export factor that stimulates nuclear protein export in permeabilized cells and undergoes nucleocytoplasmic shuttling in vivo (Black, B.E., L. Lévesque, J.M. Holaska, T.C. Wood, and B.M. Paschal. 1999. Mol. Cell. Biol. 19:8616–8624). Here, we describe the molecular characterization of NXT1 in the context of the Crm1-dependent export pathway. We find that NXT1 binds directly to Crm1, and that the interaction is sensitive to the presence of Ran-GTP. Moreover, mutations in NXT1 that reduce binding to Crm1 inhibit the activity of NXT1 in nuclear export assays. We show that recombinant Crm1 and Ran are sufficient to reconstitute nuclear translocation of a Rev reporter protein from the nucleolus to an antibody accessible site on the cytoplasmic side of the NPC. Further progress on the export pathway, including the terminal step of Crm1 and Rev reporter protein release, requires NXT1. We propose that NXT1 engages with the export complex in the nucleoplasm, and that it facilitates delivery of the export complex to a site on the cytoplasmic side of NPC where the receptor and substrate are released into the cytoplasm

A study on the relationship between orthorexia and vegetarianism using the BOT ("Bratman Test for Orthorexia")

Aim. The following article presents the relationship between vegetarianism and orthorexia nervosa (ON). Vegetarianism is an ideology and a way of life that aims at minimizing animal exploitation. A vegetarian diet excludes the consumption of meat together with other animalderived products. According to scientists, orthorexia nervosa is considered to be a new, yet unclassified eating disorder. It involves introducing dietary restrictions by individuals who feel a desire to improve their health status by healthy eating. Method. The study involved 2,611 participants, namely 1,346 vegetarians and 1,265 non-vegetarians. The research questionnaire consisted of general personal and anthropometric characteristics, the BOT (Bratman Test for Orthorexia) and questions evaluateing the participants’ attitude towards nutrition. Results. Based on the obtained results, health food fanaticism is more specific to vegetarians than non-vegetarians. The risk for orthorexia nervosa decreases with age and diet duration. The biggest number of health food fanatics was found in the group of lacto-vegetarians, a lower number among ovo-vegetarians and lacto-ovo-vegetarians, and the smallest number was observed in the vegan group. Also, vegetarians were reported to have dietary consultations as frequently as non-vegetarians. Discussion. Very few studies can be found on the relationship between orthorexia nervosa and vegetarianism. Some scientists believe that vegetarians are particularly prone to orthorexia nervosa. In addition, it has been suggested by other researchers that vegetarianism can be used to mask eating disorders, as it allows these affected individuals to avoid certain products or situations related to food. The direction of cause and effect cannot be determined

Arsenic – Poison or medicine?

Arsenic (As) is commonly known as a poison. Only a few people know that As has also been widely used in medicine. In the past years As and its compounds were used as a medicine for the treatment of such diseases as diabetes, psoriasis, syphilis, skin ulcers and joint diseases. Nowadays As is also used especially in the treatment of patients with acute promyelocytic leukemia. The International Agency for Research on Cancer (IARC) has recognized arsenic as an element with carcinogenic effect evidenced by epidemiological studies, but as previously mentioned it is also used in the treatment of neoplastic diseases. This underlines the specificity of the arsenic effects. Arsenic occurs widely in the natural environment, for example, it is present in soil and water, which contributes to its migration to food products. Long exposure to this element may lead to liver damages and also to changes in myocardium. Bearing in mind that such serious health problems can occur, monitoring of the As presence in the environmental media plays a very important role. In addition, the occupational risk of As exposure in the workplace should be identified and checked. Also the standards for As presence in food should be established. This paper presents a review of the 2015 publications based on the Medical database like PubMed and Polish Medical Bibliography. It includes the most important information about arsenic in both forms, poison and medicine. Med Pr 2016;67(1):89–9

Identification of QTLs affecting scopolin and scopoletin biosynthesis in Arabidopsis thaliana

Scopoletin and its glucoside scopolin are important secondary metabolites synthesized in plants as a defense mechanism against various environmental stresses. They belong to coumarins, a class of phytochemicals with significant biological activities that is widely used in medical application and cosmetics industry. Although numerous studies showed that a variety of coumarins occurs naturally in several plant species, the details of coumarins biosynthesis and its regulation is not well understood. It was shown previously that coumarins (predominantly scopolin and scopoletin) occur in Arabidopsis thaliana (Arabidopsis) roots, but until now nothing is known about natural variation of their accumulation in this model plant. Therefore, the genetic architecture of coumarins biosynthesis in Arabidopsis has not been studied before.Here, the variation in scopolin and scopoletin content was assessed by comparing seven Arabidopsis accessions. Subsequently, a quantitative trait locus (QTL) mapping was performed with an Advanced Intercross Recombinant Inbred Lines (AI-RILs) mapping population EstC (Est-1 × Col). In order to reveal the genetic basis of both scopolin and scopoletin biosynthesis, two sets of methanol extracts were made from Arabidopsis roots and one set was additionally subjected to enzymatic hydrolysis prior to quantification done by high-performance liquid chromatography (HPLC). We identified one QTL for scopolin and five QTLs for scopoletin accumulation. The identified QTLs explained 13.86% and 37.60% of the observed phenotypic variation in scopolin and scopoletin content, respectively. In silico analysis of genes located in the associated QTL intervals identified a number of possible candidate genes involved in coumarins biosynthesis.Together, our results demonstrate for the first time that Arabidopsis is an excellent model for studying the genetic and molecular basis of natural variation in coumarins biosynthesis in plants. It additionally provides a basis for fine mapping and cloning of the genes involved in scopolin and scopoletin biosynthesis. Importantly, we have identified new loci for this biosynthetic process

Targeting of Sna3p to the Endosomal Pathway Depends on Its Interaction with Rsp5p and Multivesicular Body Sorting on Its Ubiquitylation

Rsp5p is an ubiquitin (Ub)-protein ligase of the Nedd4 family that carries WW domains involved in interaction with PPXY-containing proteins. It plays a key role at several stages of intracellular trafficking, such as Ub-mediated internalization of endocytic cargoes and Ub-mediated sorting of membrane proteins to internal vesicles of multivesicular bodies (MVBs), a process that is crucial for their subsequent targeting to the vacuolar lumen. Sna3p is a membrane protein previously described as an Ub-independent MVB cargo, but proteomic studies have since shown it to be an ubiquitylated protein. Sna3p carries a PPXY motif. We observed that this motif mediates its interaction with Rsp5p WW domains. Mutation of either the Sna3p PPXY motif or the Rsp5p WW3 domain or reduction in the amounts of Rsp5 results in the mistargeting of Sna3p to multiple mobile vesicles and prevents its sorting to the endosomal pathway. This sorting defect appears to occur prior to the defect displayed in rsp5 mutants by other MVB cargoes, which are correctly sorted to the endosomal pathway but missorted to the vacuolar membrane instead of the vacuolar lumen. Sna3p is polyubiquitylated on one target lysine, and a mutant Sna3p lacking its target lysine displays defective MVB sorting. Sna3p undergoes Rsp5-dependent polyubiquitylation, with K63-linked Ub chains