Comparative transcriptomic analysis of chemoreceptors in two sympatric scarab beetles, Hylamorpha elegans and Brachysternus prasinus.

Chemoreception through odorant receptors (ORs), ionotropic receptors (IRs) and gustatory receptors (GRs) represents the functions of key proteins in the chemical ecology of insects. Recent studies have identified chemoreceptors in coleopterans, facilitating the evolutionary analysis of not only ORs but also IRs and GRs. Thus, Cerambycidae, Tenebrionidae and Curculionidae have received increased attention. However, knowledge of the chemoreceptors from Scarabaeidae is still limited, particularly for those that are sympatric. Considering the roles of chemoreceptors, this analysis could shed light on evolutionary processes in the context of sympatry. Therefore, the aim of this study was to identify and compare the repertoires of ORs, GRs and IRs between two sympatric scarab beetles, Hylamorpha elegans and Brachysternus prasinus. Here, construction of the antennal transcriptomes of both scarab beetle species and analyses of their phylogeny, molecular evolution and relative expression were performed. Thus, 119 new candidate chemoreceptors were identified for the first time, including 17 transcripts for B. prasinus (1 GR, 3 IRs and 13 ORs) and 102 for H. elegans (22 GRs, 14 IRs and 66 ORs). Orthologs between the two scarab beetle species were found, revealing specific expansions as well as absence in some clades. Purifying selection appears to have occurred on H. elegans and B. prasinus ORs. Further efforts will be focused on target identification to characterize kairomone and/or pheromone receptors.

Toxinas animais seletivas a canais iônicos: uma revisão / Ion channels selective animal toxins: a review

Animal poisons are glandular secretions that compromise biological systems. Their active biomolecules are called toxins. Many affect ion channels and ionotropic receptors, membrane proteins that control cellular ion flow. In this work a bibliographic survey was carried out about the main toxins of animal origin whose targets are ion channels. The groups with the highest toxin diversity were Conus ssp., Araneae, Scorpiones, Serpentes and Cnidaria. Toxins studies support basic and applied science. Despite their therapeutic potential, of all the studied poisons only ω-conotoxin MVIIA was approved for clinical use. So the field still has a lot to offer.

Venenos animais são secreções glandulares que comprometem sistemas biológicos. Suas biomoléculas ativas são denominadas toxinas. Muitas afetam canais iônicos e receptores ionotrópicos, proteínas de membrana que controlam o fluxo iônico celular. Neste trabalho foi realizado um levantamento bibliográfico sobre as principais toxinas de origem animal cujos alvos são canais iônicos. Os grupos com maior diversidade de toxinas foram Conus ssp., Araneae, Scorpiones, Serpentes e Cnidaria. Estudos sobre toxinas auxiliam a ciência de base e aplicada. Apesar do potencial terapêutico, dentre todos os venenos estudados apenas a ω-conotoxina MVIIA obteve aprovação para o uso clinico. Portanto, o campo ainda tem muito a oferecer.

The Interplay between Ca2+ Signaling Pathways and Neurodegeneration.

Calcium (Ca2+) homeostasis is essential for cell maintenance since this ion participates in many physiological processes. For example, the spatial and temporal organization of Ca2+ signaling in the central nervous system is fundamental for neurotransmission, where local changes in cytosolic Ca2+ concentration are needed to transmit information from neuron to neuron, between neurons and glia, and even regulating local blood flow according to the required activity. However, under pathological conditions, Ca2+ homeostasis is altered, with increased cytoplasmic Ca2+ concentrations leading to the activation of proteases, lipases, and nucleases. This review aimed to highlight the role of Ca2+ signaling in neurodegenerative disease-related apoptosis, where the regulation of intracellular Ca2+ homeostasis depends on coordinated interactions between the endoplasmic reticulum, mitochondria, and lysosomes, as well as specific transport mechanisms. In neurodegenerative diseases, alterations-increased oxidative stress, energy metabolism alterations, and protein aggregation have been identified. The aggregation of α-synuclein, ß-amyloid peptide (Aß), and huntingtin all adversely affect Ca2+ homeostasis. Due to the mounting evidence for the relevance of Ca2+ signaling in neuroprotection, we would focus on the expression and function of Ca2+ signaling-related proteins, in terms of the effects on autophagy regulation and the onset and progression of neurodegenerative diseases.

Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins.

Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel's ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators.

L-Glutamato: un aminoácido clave para las funciones sensoriales y metabólicas / L-glutamate: a key amino acid for sensory and metabolic functions

El ácido glutámico como tal o en su forma ionizada L-glutamato (GLU) es uno de los aminoácidos más abundantes en la naturaleza debido a que cumple funciones importantes a nivel celular y sistémico. En el intestino y el hígado, por ejemplo, el GLU constituye fuente de energía y es precursor de moléculas de relevancia biológica. Mientras que en el sistema nervioso central de los mamíferos actúa como neurotransmisor excitatorio, debido a la interacción con receptores específicos distribuidos en el cerebro. Además al GLU se le ha relacionado con la potenciación a corto y largo plazo de la memoria y el aprendizaje. Por otro lado, el consumo de GLU o de su sal monosódica (GMS) como aditivo alimentario genera el gusto umami, palabra japonesa que significa sabroso. El consumo de GMS ha sido considerado seguro por diferentes organizaciones que evalúan la inocuidad de uso de los aditivos alimentarios, razón por la cual han establecido una ingesta diaria admisible (IDA) "no especificada" y lo clasifican como un ingrediente reconocido como seguro o sustancia GRAS (por sus siglas en inglés, Generally Recognized Safe Substance). En esta revisión se presentan los aspectos del metabolismo del GLU, su papel en la degustación de los alimentos y la inocuidad del uso del GMS(AU)

Glutamic acid or its ionic form L-glutamate (GLU) is one of the most abundant amino acids in nature and it plays important functions at the cellular and systemic levels. For instance, in the intestine and liver, GLU is a source of energy and is the precursor of key biological molecules. At the central nervous system of mammals, GLU acts as an excitatory neurotransmitter due to the interaction with specific receptors. In addition, GLU has been related with short- and long-term potentiation, memory and the learning. Furthermore, consumption of GLU or its monosodium salt (monosodium glutamate, MSG) as a food additive is responsible for the umami taste. The consumption of MSG has been considered safe for different agencies responsible for the evaluation of the safe use of food additives, which have establish an Acceptable Daily Intake (ADI) “not specified”, or classified as Generally Recognized Safe Substance (GRAS). This review focuses on important metabolic aspects of GLU and its role in food tasting and MSG safety(AU)

Growth hormone (GH) increases cognition and expression of ionotropic glutamate receptors (AMPA and NMDA) in transgenic zebrafish (Danio rerio).

The growth hormone/insulin-like factor I (GH/IGF-I) somatotropic axis is responsible for somatic growth in vertebrates, and has important functions in the nervous system. Among these, learning and memory functions related to the neural expression of ionotropic glutamate receptors, mainly types AMPA (α-amino-3hydroxy-5methylisoxazole-4propionic) and NMDA (N-methyl-d-aspartate) can be highlighted. Studies on these mechanisms have been almost exclusively conducted on mammal models, with little information available on fish. Consequently, this study aimed at evaluating the effects of the somatotropic axis on learning and memory of a GH-transgenic zebrafish (Danio rerio) model (F0104 strain). Long-term memory (LTM) was tested in an inhibitory avoidance apparatus, and brain expression of igf-I and genes that code for the main subunits of the AMPA and NMDA receptors were evaluated. Results showed a significant increase in LTM for transgenic fish. Transgenic animals also showed a generalized pattern of increase in the expression of AMPA and NMDA genes, as well as a three-fold induction in igf-I expression in the brain. When analyzed together, these results indicate that GH, mediated by IGF-I, has important effects on the brain, with improvement in LTM as a result of increased glutamate receptors. The transgenic strain F0104 was shown to be an interesting model for elucidating the intricate mechanisms related to the effect of the somatotropic axis on learning and memory in vertebrates.

Estudio computacional de las relaciones evolutivas de los receptores ionotrópicos NMDA, AMPA y kainato en cuatro especies de primates / Computational study of the evolutionary relationships of the ionotropic receptors NMDA, AMPA and kainate in four species of primates / Estudo computacional das relações evolutivas dos receptores ionotrópicos NMDA, AMPA e cainato em quatro espécies de primatas

Objetivo. Identificar la influencia de los cambios respecto a la estructura secundaria y a la relación evolutiva de los receptores NMDA, AMPA Y KAINATO en las especies Homo sapiens, Pan troglodytes, Pongo pygmaeus, y Macaca mulata. Materiales y métodos. Se recopilaron 91 secuencias correspondientes a los receptores NMDA, AMPA y Kainato y se sometieron a los programas de predicción de estructura secundaria, sitios de fosforilación, alineamientos múltiples, selección del modelo de evolución y predicción filogenética. Resultados. Se encontró que las subunidades GLUR5, NR2A, NR2C y NR3A presentaron cambios de estructura en la región C-terminal y aparición o pérdida de sitios de fosforilación en esta zona. Adicionalmente la predicción filogenética nos propone que las subunidades NR2 de NMDA son las más cercanas al nodo ancestral que da origen a los demás subunidades. Conclusiones. Los cambios de estructura y sitios de fosforilación en las subunidades GLUR5, NR2A, NR2C y NR3A nos sugieren variaciones en la interacción de la región C-terminal con proteínas quinasas y con proteínas con dominios PDZ lo cual podría afectar el tráfico y anclaje de las subunidades. Por otra parte la predicción filogenética nos propone que los cambios que se presentaron en las subunidades NR2 dieron origen a las demás subunidades de los receptores ionotrópicos de glutamato, básicamente porque son las subunidades de NMDA y en particular NR2D las que se encuentran más estrechamente relacionadas con el nodo ancestral que posiblemente dio origen a los iGluRs.

Objective. To identify the influence of changes on the secondary structure and evolutionary relationship of NMDA, AMPA and kainate receptors in Homo sapiens, Pan troglodytes, Pongo pygmaeus and Macaca mulatta. Materials and methods. We identified 91 sequences for NMDA, AMPA and kainate receptors and analyzed with software for predicting secondary structure, phosphorylation sites, multiple alignments, selection of protein evolution models and phylogenetic prediction. Results. We found that subunits GLUR5, NR2A, NR2C and NR3A showed structural changes in the C-terminal region and formation or loss of phosphorylation sites in this zone. Additionally the phylogenetic prediction suggests that the NMDA NR2 subunits are the closest to the ancestral node that gives rise to the other subunits. Conclusions. Changes in structure and phosphorylation sites in GLUR5, NR2A, NR2C and NR3A subunits suggest variations in the interaction of the C-terminal region with kinase proteins and with proteins with PDZ domains, which could affect the trafficking and anchoring of the subunits. On the other hand, the phylogenetic prediction suggests that the changes that occurred in the NR2 subunits gave rise to the other subunits of glutamate ionotropic receptors, primarily because the NMDA and particularly the NR2D subunits are the most closely related to the ancestral node that possibly gave rise to the iGluRs.

Objetivo. Identificar a influência das mudanças da estrutura secundária e da relação evolutiva dos receptores NMDA, AMPA e cainato nas espécies Homo sapiens, Pan troglodytes, Pongo pygmaeus e Macaca mulatta. Materiais e métodos. Foram recopiladas 91 seqüências correspondentes aos receptores NMDA, AMPA e cainato e foram submetidos a programas de predição de estrutura secundária, sítios de fosforilação, alinhamentos múltiplos, seleção do modelo de evolução e predição da filogenia. Resultados. Descobrimos que as subunidades GLUR5, NR2A, NR2C e NR3A apresentaram alterações estruturais na região C-terminal e aparecimento ou perda de sítios de fosforilação nesta área. Além disso, a predição filogenética sugere ainda que as subunidades NR2 de NMDA são as mais próximas ao nó ancestral que dá origem às demais subunidades. Conclusões. As mudanças na estrutura e nos sítios de fosforilação nas subunidades GLUR5, NR2A, NR2C e NR3A sugerem variações na interação da região C-terminal com proteínas quinase e com proteínas de domínios PDZ que poderia afetar o tráfego e fixação das subunidades. Além disso, a predição filogenética sugere que as mudanças ocorridas nas subunidades NR2 deram origem às outras subunidades de receptores ionotrópicos de glutamato, principalmente porque são subunidade NMDA e particularmente NR2D aquelas que são mais estreitamente relacionadas com o nó ancestral que provavelmente deu origem aos iGluRs.