scholarly journals Toxin-like neuropeptides in the sea anemone Nematostella unravel recruitment from the nervous system to venom

2020 ◽  
Author(s):  
Maria Y. Sachkova ◽  
Morani Landau ◽  
Joachim M. Surm ◽  
Jason Macrander ◽  
Shir Singer ◽  
...  
Keyword(s):  
Fish Larvae ◽  
Expression Patterns ◽  
Sea Anemone ◽  
Alternative Promoters ◽  
Venom Component ◽  
Evolutionary Pathway ◽  
Cysteine Motif ◽  
Bona Fide ◽  
Regulatory Flexibility ◽  
Protein Recruitment

AbstractThe sea anemone Nematostella vectensis (Anthozoa, Cnidaria) is a powerful model system for characterizing the evolution of genes functioning in venom and nervous systems. Despite being an example for evolutionary novelty, the evolutionary origin of most toxins remains unknown. Here we report the first bona fide case of protein recruitment from the cnidarian nervous to venom system. The ShK-like1 peptide has ShKT cysteine motif, is lethal for fish larvae and packaged into nematocysts, the cnidarian venom-producing stinging capsules. Thus, ShK-like1 is a toxic venom component. Its paralog, ShK-like2, is a neuropeptide localized to neurons and is involved in development. Interestingly, both peptides exhibit similarities in their functional activities: both of them provoke contraction in Nematostella polyps and are toxic to fish. Because ShK-like2 but not ShK-like1 is conserved throughout sea anemone phylogeny, we conclude that the two paralogs originated due to a Nematostella-specific duplication of a ShK-like2 ancestor, a neuropeptide-encoding gene, followed by diversification and partial functional specialization. Strikingly, ShK-like2 is represented by two gene isoforms controlled by alternative promoters conferring regulatory flexibility throughout development. Additionally, we characterized the expression patterns of four other peptides with structural similarities to studied venom components, and revealed their unexpected neuronal localization. Thus, we employed genomics, transcriptomics and functional approaches to reveal one new venom component, five neuropeptides with two different cysteine motifs and an evolutionary pathway from nervous to venom system in Cnidaria.

scholarly journals Toxin-like neuropeptides in the sea anemoneNematostellaunravel recruitment from the nervous system to venom

2020 ◽  
Vol 117 (44) ◽  
pp. 27481-27492
Author(s):  
Maria Y. Sachkova ◽  
Morani Landau ◽  
Joachim M. Surm ◽  
Jason Macrander ◽  
Shir A. Singer ◽  
...  
Keyword(s):  
Fish Larvae ◽  
Expression Patterns ◽  
Sea Anemone ◽  
Alternative Promoters ◽  
Venom Component ◽  
Evolutionary Pathway ◽  
Ancestral Gene ◽  
Cysteine Motif ◽  
Regulatory Flexibility ◽  
Protein Recruitment

The sea anemoneNematostella vectensis(Anthozoa, Cnidaria) is a powerful model for characterizing the evolution of genes functioning in venom and nervous systems. Although venom has evolved independently numerous times in animals, the evolutionary origin of many toxins remains unknown. In this work, we pinpoint an ancestral gene giving rise to a new toxin and functionally characterize both genes in the same species. Thus, we report a case of protein recruitment from the cnidarian nervous to venom system. The ShK-like1 peptide has a ShKT cysteine motif, is lethal for fish larvae and packaged into nematocysts, the cnidarian venom-producing stinging capsules. Thus, ShK-like1 is a toxic venom component. Its paralog, ShK-like2, is a neuropeptide localized to neurons and is involved in development. Both peptides exhibit similarities in their functional activities: They provoke contraction inNematostellapolyps and are toxic to fish. Because ShK-like2 but not ShK-like1 is conserved throughout sea anemone phylogeny, we conclude that the two paralogs originated due to aNematostella-specific duplication of a ShK-like2 ancestor, a neuropeptide-encoding gene, followed by diversification and partial functional specialization. ShK-like2 is represented by two gene isoforms controlled by alternative promoters conferring regulatory flexibility throughout development. Additionally, we characterized the expression patterns of four other peptides with structural similarities to studied venom components and revealed their unexpected neuronal localization. Thus, we employed genomics, transcriptomics, and functional approaches to reveal one venom component, five neuropeptides with two different cysteine motifs, and an evolutionary pathway from nervous to venom system in Cnidaria.

scholarly journals Alternatively spliced isoforms reveal a novel type of PTB domain in CCM2 protein

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Xiaoting Jiang ◽  
Akhil Padarti ◽  
Yanchun Qu ◽  
Shen Sheng ◽  
Johnathan Abou-Fadel ◽  
...  
Keyword(s):  
Genomic Structure ◽  
Expression Patterns ◽  
Genetic Mutation ◽  
Protein Isoforms ◽  
Start Codon ◽  
Transcriptional Level ◽  
Alternative Promoters ◽  
Cavernous Malformations ◽  
Cellular Expression ◽  
Ptb Domain

Abstract Cerebral cavernous malformations (CCMs) is a microvascular disorder in the central nervous system. Despite tremendous efforts, the causal genetic mutation in some CCM patients has not be identified, raising the possibility of an unknown CCM locus. The CCM2/MGC4607 gene has been identified as one of three known genes causing CCMs. In this report, we defined a total of 29 novel exons and 4 novel promoters in CCM2 genomic structure and subsequently identified a total of 50 new alternative spliced isoforms of CCM2 which eventually generated 22 novel protein isoforms. Genetic analysis of CCM2 isoforms revealed that the CCM2 isoforms can be classified into two groups based on their alternative promoters and alternative start codon exons. Our data demonstrated that CCM2 isoforms not only are specific in their subcellular compartmentation but also have distinct cellular expression patterns among various tissues and cells, indicating the pleiotropic cellular roles of CCM2 through their multiple isoforms. In fact, the complexity of the CCM2 genomic structure was reflected by the multiple layers of regulation of CCM2 expression patterns. At the transcriptional level, it is accomplished by alternative promoters, alternative splicing, and multiple transcriptional start sites and termination sites; while at the translational level, it is carried out with various cellular functions with a distinguishable CCM2 protein group pattern, specified abundance and composition of selective isoforms in a cell and tissue specific fashion. Through experimentation, we discovered a unique phosphotyrosine binding (PTB) domain, namely atypical phosphotyrosine binding (aPTB) domain. Some long CCM2 isoform proteins contain both classes of PTB domains, making them a dual PTB domain-containing protein. Both CCM1 and CCM3 can bind competitively to this aPTB domain, indicating CCM2 as the cornerstone for CCM signaling complex (CSC).

scholarly journals EXPLICIT-Kinase: a gene expression predictor for dissecting the functions of the Arabidopsis kinome

2021 ◽  
Author(s):  
Yuming Peng ◽  
Wanzhu Zuo ◽  
Yue Qin ◽  
Shisong Ma
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Protein Kinases ◽  
Stress Responses ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
The Novel ◽  
Cellular Processes ◽  
Bona Fide ◽  
Kinase A

Protein kinases regulate virtually all cellular processes, but it remains challenging to determine the functions of all protein kinases, collectively called the kinome, in any species. We developed an approach called EXPLICIT-Kinase to predict the functions of the Arabidopsis kinome. Because the activities of many kinases can be regulated transcriptionally, their gene expression patterns provide clues to their functions. A universal gene expression predictor for Arabidopsis was constructed to predict the expression of 30,172 non-kinase genes based on the expression of 994 protein kinase genes. The model reconstituted highly accurate transcriptomes for diverse Arabidopsis samples. It identified the significant kinases as predictor kinases for predicting the expression of Arabidopsis genes and pathways. Strikingly, these predictor kinases were often known regulators of the related pathways, as exemplified by those involved in cytokinesis, tissue development, and stress responses. Comparative analyses have revealed that portions of these predictor kinases, including the novel ones, are shared and conserved between Arabidopsis and maize. The conservation between species provide additional evidence to support the novel predictor kinases as bona fide regulators of the pathways involved. Thus our approach enables the systematic dissection of the functions of the Arabidopsis kinome.

scholarly journals Characterization of Venom Components and Their Phylogenetic Properties in Some Aculeate Bumblebees and Wasps

Toxins ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 47
Author(s):  
Kyungjae Andrew Yoon ◽  
Kyungmun Kim ◽  
Woo-Jin Kim ◽  
Woo Young Bang ◽  
Neung-Ho Ahn ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Arginine Kinase ◽  
Housekeeping Gene ◽  
Venom Gland ◽  
Social Wasps ◽  
Venom Component ◽  
Wasp Species ◽  
Bumblebee Species ◽  
Venom Glands ◽  
Behavioral Influences

To identify and compare venom components and expression patterns, venom gland-specific transcriptome analyses were conducted for 14 Aculeate bees and wasps. TPM (transcripts per kilobase million) values were normalized using the average transcription level of a reference housekeeping gene (dimethyladenosine transferase). Orthologous venom component genes across the 14 bee and wasp species were identified, and their relative abundance in each species was determined by comparing normalized TPM values. Based on signal sequences in the transcripts, the genes of novel venom components were identified and characterized to encode potential allergens. Most of the allergens and pain-producing factors (arginine kinase, hyaluronidase, mastoparan, phospholipase A1, phospholipase A2, and venom allergen 5) showed extremely high expression levels in social wasps. Acid phosphatase, neprilysin, and tachykinin, which are known allergens and neurotoxic peptides, were found in the venom glands of solitary wasps more often than in social wasps. In the venom glands of bumblebees, few or no transcripts of major allergens or pain-producing factors were identified. Taken together, these results indicate that differential expression patterns of the venom genes in some Aculeate species imply that some wasps and bumblebee species have unique groups of highly expressed venom components. Some venom components reflected the Aculeate species phylogeny, but others did not. This unique evolution of specific venom components in different groups of some wasps and bumblebee species might have been shaped in response to both ecological and behavioral influences.

scholarly journals Enigma of Retrotransposon Biology in Mammalian Early Embryos and Embryonic Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Ying Yin ◽  
Liquan Zhou ◽  
Shuiqiao Yuan
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Alternative Promoters ◽  
Human Escs ◽  
Early Embryos ◽  
Regulatory Functions

Retrotransposons comprise a significant fraction of mammalian genome with unclear functions. Increasing evidence shows that they are not just remnants of ancient retroviruses but play important roles in multiple biological processes. Retrotransposons are epigenetically silenced in most somatic tissues and become reactivated in early embryos. Notably, abundant retrotransposon expression in mouse embryonic stem cells (ESCs) marks transient totipotency status, while retrotransposon enrichment in human ESCs indicates naive-like status. Some retrotransposon elements retained the capacity to retrotranspose, such as LINE1, producing genetic diversity or disease. Some other retrotransposons reside in the vicinity of endogenous genes and are capable of regulating nearby genes and cell fate, possibly through providing alternative promoters, regulatory modules, or orchestrating high-order chromatin assembly. In addition, retrotransposons may mediate epigenetic memory, regulate gene expression posttranscriptionally, defend virus infection, and so on. In this review, we summarize expression patterns and regulatory functions of different retrotransposons in early embryos and ESCs, as well as document molecular mechanisms controlling retrotransposon expression and their potential functions. Further investigations on the regulatory network of retrotransposons in early embryogenesis and ESCs will provide valuable insights and a deeper understanding of retrotransposon biology. Additionally, endeavors made to unveil the roles of these mysterious elements may facilitate stem cell status conversion and manipulation of pluripotency.

scholarly journals Identification of a Methylation Imprint Mark within the Mouse Gnas Locus

2000 ◽  
Vol 20 (16) ◽  
pp. 5808-5817 ◽  
Author(s):  
Jie Liu ◽  
Shuhua Yu ◽  
Deborah Litman ◽  
Weiping Chen ◽  
Lee S. Weinstein
Keyword(s):  
Expression Patterns ◽  
Differential Methylation ◽  
Upstream Region ◽  
Gene Products ◽  
Alternative Promoters ◽  
Promoter Regions ◽  
Α Subunit ◽  
Somatic Tissues ◽  
Specific Mrnas ◽  
Translational Start

ABSTRACT The imprinted mouse gene Gnas produces the G protein α-subunit GSα and several other gene products by using alternative promoters and first exons. GSα is maternally expressed in some tissues and biallelically expressed in most other tissues, while the gene products NESP55 and XLαs are maternally and paternally expressed, respectively. We investigated the mechanisms of Gnas imprinting. The GSα promoter and first exon are not methylated on either allele. A further upstream region (approximately from positions −3400 to −939 relative to the GSα translational start site) is methylated only on the maternal allele in all adult somatic tissues and in early postimplantation development. Within this region lies a fourth promoter and first exon (exon 1A) that generates paternal-specific mRNAs of unknown function. Exon 1A and GSα mRNAs have similar expression patterns, making competition between their promoters unlikely. Differential methylation in this region is established during gametogenesis, being present in oocytes and absent in spermatozoa, and is maintained in preimplantation E3.5d blastocysts. Therefore, this region is a methylation imprint mark. In contrast, differential methylation of the NESP55 and XLαs promoter regions (Nespand Gnasxl) is not established during gametogenesis. The methylation imprint mark that we identified may be important for the tissue-specific imprinting of GSα.

scholarly journals Tissue-Specific and Ubiquitous Expression Patterns from Alternative Promoters of Human Genes

PLoS ONE ◽  
2010 ◽  
Vol 5 (8) ◽  
pp. e12274 ◽  
Author(s):  
Edwin Jacox ◽  
Valer Gotea ◽  
Ivan Ovcharenko ◽  
Laura Elnitski
Keyword(s):  
Expression Patterns ◽  
Alternative Promoters ◽  
Tissue Specific ◽  
Human Genes

scholarly journals Insights into coral bleaching under heat stress from analysis of gene expression in a sea anemone model system

2020 ◽  
Vol 117 (46) ◽  
pp. 28906-28917
Author(s):  
Phillip A. Cleves ◽  
Cory J. Krediet ◽  
Erik M. Lehnert ◽  
Masayuki Onishi ◽  
John R. Pringle
Keyword(s):  
Gene Expression ◽  
Innate Immunity ◽  
Transcription Factors ◽  
Heat Stress ◽  
Expression Patterns ◽  
Model System ◽  
Sea Anemone ◽  
Transcript Levels ◽  
Early Stress ◽  
Endosymbiotic Algae

Loss of endosymbiotic algae (“bleaching”) under heat stress has become a major problem for reef-building corals worldwide. To identify genes that might be involved in triggering or executing bleaching, or in protecting corals from it, we used RNAseq to analyze gene-expression changes during heat stress in a coral relative, the sea anemone Aiptasia. We identified >500 genes that showed rapid and extensive up-regulation upon temperature increase. These genes fell into two clusters. In both clusters, most genes showed similar expression patterns in symbiotic and aposymbiotic anemones, suggesting that this early stress response is largely independent of the symbiosis. Cluster I was highly enriched for genes involved in innate immunity and apoptosis, and most transcript levels returned to baseline many hours before bleaching was first detected, raising doubts about their possible roles in this process. Cluster II was highly enriched for genes involved in protein folding, and most transcript levels returned more slowly to baseline, so that roles in either promoting or preventing bleaching seem plausible. Many of the genes in clusters I and II appear to be targets of the transcription factors NFκB and HSF1, respectively. We also examined the behavior of 337 genes whose much higher levels of expression in symbiotic than aposymbiotic anemones in the absence of stress suggest that they are important for the symbiosis. Unexpectedly, in many cases, these expression levels declined precipitously long before bleaching itself was evident, suggesting that loss of expression of symbiosis-supporting genes may be involved in triggering bleaching.

Does PtdIns(4,5)P2 concentrate so it can multi-task?

2016 ◽  
Vol 44 (1) ◽  
pp. 228-233 ◽  
Author(s):  
Gerald R.V. Hammond
Keyword(s):  
Protein Complexes ◽  
Second Messengers ◽  
Open Questions ◽  
Signalling Molecule ◽  
Health And Disease ◽  
Bona Fide ◽  
Experimental Approaches ◽  
Structural Lipid ◽  
A Minor ◽  
Protein Recruitment

Ptdns(4,5)P2 is a minor structural lipid of the plasma membrane (PM), but a master regulator of PM function. Serving either as a substrate for the generation of second messengers, or more commonly as a ligand triggering protein recruitment or activation, it regulates most aspects of PM function. Understanding how this relatively simple biological macromolecule can regulate such a vast array of different functions in parallel, is the key to understanding the biology of the PM as a whole, in both health and disease. In this review, potential mechanisms are discussed that might explain how a lipid can separately regulate so many protein complexes. The focus is on the spatial distribution of the lipid molecules, their metabolism and their interactions. Open questions that still need to be resolved are highlighted, as are potential experimental approaches that might shed light on the mechanisms at play. Moreover, the broader question is raised as to whether PtdIns(4,5)P2 should be thought of as a bona fide signalling molecule or more of a simple lipid cofactor or perhaps both, depending on the context of the particular function in question.

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