Nitric oxide in invertebrates

Nitric oxide (NO) is considered an important signaling molecule implied in different physiological processes, including nervous transmission, vascular regulation, immune defense, and in the pathogenesis of several diseases. The presence of NO is well demonstrated in all vertebrates. The recent data on the presence and roles of NO in the main invertebrate groups are reviewed here, showing the widespread diffusion of this signaling molecule throughout the animal kingdom, from higher invertebrates down to coelenterates and even to prokaryotic cells. In invertebrates, the main functional roles described for mammals have been demonstrated, whereas experimental evidence suggests the presence of new NOS isoforms different from those known for higher organisms. Noteworthy is the early appearance of NO throughout evolution and striking is the role played by the nitrergic pathway in the sensorial functions, from coelenterates up to mammals, mainly in olfactory-like systems. All literature data here reported suggest that future research on the biological roles of early signaling molecules in lower living forms could be important for the understanding of the nervous-system evolution.     

The Biphasic Life Cycle--A Central Theme of Metazoan Evolution

SYNOPSIS. A life cycle alternating between a microscopic larva(mmsized) and macroscopic adult (cm-sized) occurs commonly amonginvertebrates. The pattern of occurrence of such a biphasiclife cycle among lower metazoans like the Porifera and Cnidaria,as well as ultrastructure of larva and adults of many invertebrates,suggests that the earliest phases of metazoan evolution alsohad such a cycle. Only the dispersive larvae in the originalmetazoans could be characterized as "small and mobile" if wefollow this model to its logical conclusion; the adults, bycontrast, evolved into larger-bodied organisms to maximize reproductionand were non-motile filter feeders for the most part. The biphasiclife cycle arose early in evolution, then, shortly after thefirst multicellular organisms evolved as clones of flagellatedcells linked together by interactions through ECM; selectivepressures acting independently on the two phases of the lifecycle led to the origin of the different metazoan tissue types—epithelial,connective, nervous, and muscle tissues. For the Bilateria,this suggests that extant acoelomate and pseudocoelomate formsevolved through progenesis of larvae and juveniles in a mannerlike that known for the radiation of the interstitial annelids.A better understanding of larval biology and of mechanisms forheterochrony is crucial for hypotheses of metazoan evolution.     

Highly Conserved Caspase and Bcl-2 Homologues from the Sea Anemone Aiptasia pallida: Lower Metazoans as Models for the Study of Apoptosis Evolution

Key insight into the complexities of apoptosis may be gained from the study of its evolution in lower metazoans. In this study we describe two genes from a cnidarian, Aiptasia pallida, that are homologous to key genes in the apoptotic pathway from vertebrates. The first is a novel ancient caspase, acasp, that displays attributes of both initiator and executioner caspases and includes a caspase recruitment domain (CARD). The second, a Bcl-2 family member, abhp, contains a BH1 and BH2 domain and shares structural characteristics and phylogenetic affinity with a group of antiapoptotic Bcl-2s including A1 and Bcl-2L10. The breadth of occurrence of other invertebrate homologues across the phylogenetic trees of both genes suggests that the complexity of apoptotic pathways is an ancient trait that predates the evolution of vertebrates and higher invertebrates such as nematodes and flies. This paves the way for establishing new lower metazoan model systems for the study of apoptosis. Electronic Supplementary Material Electronic Supplementary material is available for this article at and accessible for authorised users. [Reviewing Editor: Dr. Stuart Newfeld]     

Nitric oxide in marine invertebrates: a comparative perspective

Since the discovery of the biological effects of nitric oxide (NO) more than two decades ago, NO has been identified as an important physiological modulator and a messenger molecule in mammals. Parallel to these studies, evidence that has accumulated in recent years has revealed that the NO signalling pathway is spread throughout the entire phylogenetic scale, being increasingly found in lower organisms, ranging from Chordata to Mollusca. The present review attempts to provide a survey of current knowledge of the genesis and possible roles of NO and the related signalling pathway in marine invertebrates, with special emphasis on Sepia, a choice dictated by the increasing appreciation of cephalopods as most valuable model systems for studies of NO biology and the present expectation for new exciting insights into as yet little explored segments of NO biology.     

Caspase-like protease involvement in the control of plant cell death

Cell death as a highly regulated process has now been recognized to be an important, if not essential, pathway that is ubiquitous in all multicellular eukaryotes. In addition to playing key roles in the morphogenesis and sculpting of the organs to give rise to highly specialized forms and shapes, cell death also participates in the programmed creation of specialized cell types for essential functions such as the selection of B cells in the immune system of mammals and the formation of tracheids in the xylem of vascular plants. Studies of apoptosis, the most well-characterized form of animal programmed cell death, have culminated in the identification of a central tripartite death switch the enzymatic component of which is a conserved family of cysteine proteases called caspases. Studies in invertebrates and other animal models suggest that caspases are conserved regulators of apoptotic cell death in all metazoans. In plant systems, the identities of the main executioners that orchestrate cell death remain elusive. Recent evidence from inhibitor studies and biochemical approaches suggests that caspase-like proteases may also be involved in cell death control in higher plants. Furthermore, the mitochondrion and reactive oxygen species may well constitute a common pathway for cell death activation in both animal and plant cells. Cloning of plant caspase-like proteases and elucidation of the mechanisms through which mitochondria may regulate cell death in both systems should shed light on the evolution of cell death control in eukaryotes and may help to identify essential components that are highly conserved in eukaryotes.     

Slow Mitochondrial COI Sequence Evolution at the Base of the Metazoan Tree and Its Implications for DNA Barcoding

The evolution rates of mtDNA in early metazoans hold important implications for DNA barcoding. Here, we present a comprehensive analysis of intra- and interspecific COI variabilities in Porifera and Cnidaria (separately as Anthozoa, Hydrozoa, and Scyphozoa) using a data set of 619 sequences from 224 species. We found variation within and between species to be much lower in Porifera and Anthozoa compared to Medusozoa (Hydrozoa and Scyphozoa), which has divergences similar to typical metazoans. Given that recent evidence has shown that fungi also exhibit limited COI divergence, slow-evolving mtDNA is likely to be plesiomorphic for the Metazoa. Higher rates of evolution could have originated independently in Medusozoa and Bilateria or been acquired in the Cnidaria + Bilateria clade and lost in the Anthozoa. Low identification success and substantial overlap between intra- and interspecific COI distances render the Anthozoa unsuitable for DNA barcoding. Caution is also advised for Porifera and Hydrozoa because of relatively low identification success rates as even threshold divergence that maximizes the “barcoding gap” does not improve identification success. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Distribution of opine dehydrogenases and lactate dehydrogenase activities in marine animals

• 1.1. Opine dehydrogenases (OpDHs) and lactate dehydrogenase (LDH) activities were determined in various marine animals. OpDHs were detected in six marine invertebrate phyla; Porifera, Coelenterata, Annelida, Mollusca, Arthropoda and Echinodermata in phylogenic sequence.
• 2.2. Among several OpDHs, tauropine dehydrogenase (TaDH) occurred widely in marine invertebrates, from Porifera to Echinodermata.
• 3.3. With a few exceptions, total OpDHs activities exceeded that of LDH activity in the marine invertebrates investigated.
• 4.4. With respect to anaerobic glycolysis, OpDHs are indicated to play an important role in phylogenically lower invertebrates, whereas LDH is more important in higher animals.

     

Independent origins of neurons and synapses: insights from ctenophores

There is more than one way to develop neuronal complexity, and animals frequently use different molecular toolkits to achieve similar functional outcomes. Genomics and metabolomics data from basal metazoans suggest that neural signalling evolved independently in ctenophores and cnidarians/bilaterians. This polygenesis hypothesis explains the lack of pan-neuronal and pan-synaptic genes across metazoans, including remarkable examples of lineage-specific evolution of neurogenic and signalling molecules as well as synaptic components. Sponges and placozoans are two lineages without neural and muscular systems. The possibility of secondary loss of neurons and synapses in the Porifera/Placozoa clades is a highly unlikely and less parsimonious scenario. We conclude that acetylcholine, serotonin, histamine, dopamine, octopamine and gamma-aminobutyric acid (GABA) were recruited as transmitters in the neural systems in cnidarian and bilaterian lineages. By contrast, ctenophores independently evolved numerous secretory peptides, indicating extensive adaptations within the clade and suggesting that early neural systems might be peptidergic. Comparative analysis of glutamate signalling also shows numerous lineage-specific innovations, implying the extensive use of this ubiquitous metabolite and intercellular messenger over the course of convergent and parallel evolution of mechanisms of intercellular communication. Therefore: (i) we view a neuron as a functional character but not a genetic character, and (ii) any given neural system cannot be considered as a single character because it is composed of different cell lineages with distinct genealogies, origins and evolutionary histories. Thus, when reconstructing the evolution of nervous systems, we ought to start with the identification of particular cell lineages by establishing distant neural homologies or examples of convergent evolution. In a corollary of the hypothesis of the independent origins of neurons, our analyses suggest that both electrical and chemical synapses evolved more than once.     

Conserved insulin signaling in the regulation of oocyte growth,development, and maturation

Insulin signaling regulates various aspects of physiology, such as glucose homeostasis and aging, and is a key determinant of female reproduction in metazoans. That insulin signaling is crucial for female reproductive health is clear from clinical data linking hyperinsulinemic and hypoinsulinemic condition with certain types of ovarian dysfunction, such as altered steroidogenesis, polycystic ovary syndrome, and infertility. Thus, understanding the signaling mechanisms that underlie the control of insulin‐mediated ovarian development is important for the accurate diagnosis of and intervention for female infertility. Studies of invertebrate and vertebrate model systems have revealed the molecular determinants that transduce insulin signaling as well as which biological processes are regulated by the insulin‐signaling pathway. The molecular determinants of the insulin‐signaling pathway, from the insulin receptor to its downstream signaling components, are structurally and functionally conserved across evolution, from worms to mammals—yet, physiological differences in signaling still exist. Insulin signaling acts cooperatively with gonadotropins in mammals and lower vertebrates to mediate various aspects of ovarian development, mainly owing to evolution of the endocrine system in vertebrates. In contrast, insulin signaling in Drosophila and Caenorhabditis elegans directly regulates oocyte growth and maturation. In this review, we compare and contrast insulin‐mediated regulation of ovarian functions in mammals, lower vertebrates, C. elegans, and Drosophila, and highlight conserved signaling pathways and regulatory mechanisms in general while illustrating insulin's unique role in specific reproductive processes.     

Molecular and functional evidence for early divergence of an endothelin-like system during metazoan evolution: analysis of the Cnidarian, hydra

A novel putative endothelin-converting enzyme (ECE) has been cloned from hydra, a freshwater invertebrate that belongs to the second oldest phylum of the animal kingdom. As an integral component of the endothelin system, vertebrate ECE functions in the activation of endothelin (ET) peptides. Vertebrate ETs are (1) the most potent vasoconstrictors known in mammals; and (2) function as essential signaling ligands during development of tissues derived from neural crest cells. To date, only a limited number of immunocytochemical studies have suggested the presence of endothelin-like peptides in invertebrates. Based on structural and functional analyses, we present evidence for a functional endothelin-like system in hydra that is involved in both muscle contraction and developmental processes. These findings indicate the broad use of endothelin systems in metazoans and also indicate that this type of signaling system arose early in evolution even before divergence of protostomes and deuterostomes.     

Identification of a Hydra homologue of the β-catenin/plakoglobin/armadillo gene family

The β-catenin/plakoglobin/armadillo gene family encodes a group of highly conserved proteins which play important roles in cadherin-mediated cell adhesion and in signal transduction mechanisms involved in regulating development. This gene family previously had been isolated only from higher metazoans. Here, we describe the isolation and characterization of a β-catenin (βCtn) homologue from Hydra magnipapillata a diploblastic lower metazoan. Comparison of the putative amino acid (aa) sequence of Hydra βCtn, with its homologues in higher metazoans, shows that a repeating 42-aa motif present in its central domain is highly conserved throughout the metazoa. This suggests that βCtn appeared very early in metazoan evolution, possibly when primitive multicellular animals started to form epithelial cell layers.     

The Trichoplax PaxB gene: a putative Proto-PaxA/B/C gene predating the origin of nerve and sensory cells

Pax genes play key regulatory roles in embryonic and sensory organ development in metazoans but their evolution and ancestral functions remain widely unresolved. We have isolated a Pax gene from Placozoa, beside Porifera the only metazoan phylum that completely lacks nerve and sensory cells or organs. These simplest known metazoans also lack any kind of symmetry, organs, extracellular matrix, basal lamina, muscle cells, and main body axis. The isolated Pax gene from Trichoplax adhaerens harbors a paired domain, an octapeptide, and a full-length homeodomain. It displays structural features not only of PaxB and Pax2/5/8-like genes but also of PaxC and Pax6 genes. Conserved splice sites between Placozoa, Cnidaria, and triploblasts, mark the ancient origin of intron structures. Phylogenetic analyses demonstrate that the Trichoplax PaxB gene, TriPaxB, is basal not only to all other known PaxB genes but also to PaxA and PaxC genes and their relatives in triploblasts (namely Pax2/5/8, Pax4/6, and Poxneuro). TriPaxB is expressed in distinct cell patches near the outer edge of the animal body, where undifferentiated and possibly multipotent cells are found. This expression pattern indicates a developmental role in cell-type specification and/or differentiation, probably in specifying-determining fiber cells, which are regarded as proto-neural/muscle cells in Trichoplax. While PaxB, Pax2/5/8, and Pax6 genes have been linked to nerve cell and sensory system/organ development in virtually all animals investigated so far, our study suggests that Pax genes predate the origin of nerve and sensory cells.     

鱼类Toll样受体及其信号传导的研究进展

鱼类是脊椎动物中的一个重要类群, 在其生存与进化的过程中, 免疫系统担负着保护鱼类免受病原感染的重任, 其中Toll样受体家族等介导的先天性免疫是鱼类抗病免疫的第一道防线, 并在连接先天性免疫与获得性免疫反应中起着桥梁作用. 虽然从无脊椎动物到高等脊椎动物, Toll样受体家族内多数成员在蛋白质结构与功能上都较为保守, 但是鱼类作为最低等的脊椎动物, 在其进化过程中又形成了一些特有Toll样受体分子, 其剪接类型也更丰富; 鱼类Toll样受体家族介导的免疫识别、免疫信号传导、激活和调控方式与高等脊椎动物也不尽相同. 文章主要综述了鱼类Toll样受体的结构、种类、功能、多样性、免疫信号传导及其调控特点, 为深入了解鱼类的免疫反应奠定基础.       

Genome analysis of the unicellular green alga Chlamydomonas reinhardtii Indicates an ancient evolutionary origin for key pattern recognition and cell-signaling protein families

The evolution of specific cell signaling and adhesion domains may have played an important role in the transition to a multicellular existence in the metazoans. Genomic analysis indicates that several signaling domains predominately found in animals are also present in the unicellular green alga, Chlamydomonas reinhardtii. A large group of proteins is present, containing scavenger receptor cysteine-rich (SRCR) and C-type lectin domains, which function in ligand binding and play key roles in the innate immune system of animals. Chlamydomonas also contains a large family of putative tyrosine kinases, suggesting an important role for phosphotyrosine signaling in the green algae. These important signaling domains may therefore be widespread among eukaryotes and most probably evolved in ancestral eukaryotes before the divergence of the Opisthokonts (the animal and fungal lineage).     

棘皮动物免疫学研究进展

棘皮动物属原始后口动物、无脊椎动物的最高等类群,它处于由无脊椎动物向脊椎动物开始分支进化的阶段．研究棘皮动物的免疫功能和作用机理,对从比较免疫学角度探讨动物免疫系统进化过程有承前启后的重要意义．因此,有必要对棘皮动物的免疫学研究进展作一个较全面的综述,并理清未来的研究热点和方向．棘皮动物与其他无脊椎动物一样具有先天性免疫系统,但未发现脊椎动物所具有的获得性免疫．其免疫应答是由参与免疫反应的效应细胞——体腔细胞和多种体液免疫因子共同介导的．比较免疫学分析表明,棘皮动物存在脊椎动物补体系统的替代途径和凝集素途径,但未发现经典途径和明确的终端途径．棘皮动物先天性免疫系统存在数量庞大的基因家族．今后应加强对未知免疫相关基因、蛋白质、信号传导途径及效应分子的研究,回答免疫系统的起源、功能和进化等问题．     

Nitric oxide signaling in invertebrates

Nitric oxide (NO) is an unconventional neurotransmitter and neuromodulator molecule that is increasingly found to have important signaling functions in animals from nematodes to mammals. NO signaling mechanisms in the past were identified largely through experiments on mammals, after the discovery of NO's vasodilatory functions. The use of gene knock out mice has been particularly important in revealing the functions of the several isoforms of nitric oxide synthase (NOS), the enzyme that produces NO. Recent studies have revealed rich diversity in NO signaling. In addition to the well-established pathway in which NO activates guanylyl cyclase and cGMP production, redox mechanisms involving protein nitrosylation are important contributors to modulation of neurotransmitter release and reception. NO signaling studies in invertebrates are now generating a wealth of comparative information. Invertebrate NOS isoforms have been identified in insects and molluscs, and the conserved and variable amino acid sequences evaluated. Calcium-calmodulin dependence and cofactor requirements are conserved. NADPH diaphorase studies show that NOS is found in echinoderms, coelenterates, nematodes, annelids, insects, crustaceans and molluscs. Accumulating evidence reveals that NO is used as an orthograde transmitter and cotransmitter, and as a modulator of conventional transmitter release. NO appears to be used in diverse animals for certain neuronal functions, such as chemosensory signalin, learning, and development, suggesting that these NO functions have been conserved during evolution. The discovery of NO's diverse and unconventional signaling functions has stimulated a plethora of enthusiastic investigations into its uses. We can anticipate the discovery of many more interesting and some surprising NO signaling functions.     

Genomic insights into mediator lipidomics

G protein-coupled receptors (GPCR) are used ubiquitously and widely for signal transduction across the plasma membrane. The ligands for GPCRs are structurally diverse and include peptides, odorants, photon, ions and lipids. It is thought that GPCRs evolved by gene duplication and mutational events that diversified the ligand binding and signaling properties, thereby resulting in paralogues in various organisms. Genomic sequencing efforts of various organisms indicate that GPCRs evolved very early in evolution; for example, unicellular eukaryotes use GPCRs for mating, differentiation and sporulation responses and prokarotes utilize these receptors for phototransduction, as exemplified by the bacteriorhodopsin, a photon sensor. Many GPCRs fall into subfamilies, usually determined by structural similarity to their ligands. Bioactive lipids such as lysophospholipids, eicosanoids, ether lipids and endocannabinoids, which are produced widely in evolution, also signal through GPCRs. Thus, distinct subfamilies of bioactive lipid GPCRs, such as prostanoid receptors, lysophosphatidic, sphingosine 1-phosphate, leukotrienes, hydroxy fatty acids, endocannabinoids and ether lipids exist in the mammalian genome. With the increasing availability of genomic information throughout the phylogenetic tree, orthologues of bioactive lipid receptors are found in the genomes of vertebrates and chordates but not in worms, flies or other lower organisms. This is in contrast to GPCRs for biogenic amines and polypeptide growth factors, which are conserved in invertebrates as well. Thus, it appears that with the evolution of chordates, lipids may have acquired novel roles in cell-cell communication events via GPCRs. This hypothesis will be discussed using the prostanoid and lysophospholipid signaling systems. Since such bioactive lipids play critical roles in immune, vascular and nervous systems, this suggests that lipid metabolite signaling via the GPCRs co-evolved with the development of sophisticated vascular, immune and nervous systems in chordates and vertebrates.     

The endocannabinoid system in invertebrates

What is the role of the cannabinoid system in invertebrates and can it tell us something about the human system? We discuss in this review the possible presence of the cannabinoid system in invertebrates. Endocannabinoid processes, i.e., enzymatic hydrolysis, as well as cannabinoid receptors and endocannabinoids, have been identified in various species of invertebrates. These signal molecules appear to have multiple roles in invertebrates; diminishing sensory input, control of reproduction, feeding behavior, neurotransmission and antiinflammatory actions. We propose that since this system worked so well, it was retained during evolution, and that invertebrates can serve as a model to study endogenous cannabinoid signaling.