Brain inflammation generally accompanies and accelerates neurodegeneration. Here we report a microglial mechanism in which polyglutamine binding protein 1 (PQBP1) senses extrinsic tau 3R/4R proteins ...by direct interaction and triggers an innate immune response by activating a cyclic GMP-AMP synthase (cGAS)-Stimulator of interferon genes (STING) pathway. Tamoxifen-inducible and microglia-specific depletion of PQBP1 in primary culture in vitro and mouse brain in vivo shows that PQBP1 is essential for sensing-tau to induce nuclear translocation of nuclear factor κB (NFκB), NFκB-dependent transcription of inflammation genes, brain inflammation in vivo, and eventually mouse cognitive impairment. Collectively, PQBP1 is an intracellular receptor in the cGAS-STING pathway not only for cDNA of human immunodeficiency virus (HIV) but also for the transmissible neurodegenerative disease protein tau. This study characterises a mechanism of brain inflammation that is common to virus infection and neurodegenerative disorders.
Although numerous dinoflagellate species (Family Symbiodiniaceae) are present in coral reef environments, Acropora corals tend to select a single species, Symbiodinium microadriaticum, in early life ...stages, even though this species is rarely found in mature colonies. In order to identify molecular mechanisms involved in initial contact with native symbionts, we analyzed transcriptomic responses of Acropora tenuis larvae at 1, 3, 6, 12, and 24 h after their first contact with S. microadriaticum, as well as with non-native symbionts, including the non-symbiotic S. natans and the occasional symbiont, S. tridacnidorum. Some gene expression changes were detected in larvae inoculated with non-native symbionts at 1 h post-inoculation, but those returned to baseline levels afterward. In contrast, when larvae were exposed to native symbionts, we found that the number of differentially expressed genes gradually increased in relation to inoculation time. As a specific response to native symbionts, upregulation of pattern recognition receptor-like and transporter genes, and suppression of cellular function genes related to immunity and apoptosis, were exclusively observed. These findings indicate that coral larvae recognize differences between symbionts, and when the appropriate symbionts infect, they coordinate gene expression to establish stable mutualism.
Abstract
The genus Acropora comprises the most diverse and abundant scleractinian corals (Anthozoa, Cnidaria) in coral reefs, the most diverse marine ecosystems on Earth. However, the genetic basis ...for the success and wide distribution of Acropora are unknown. Here, we sequenced complete genomes of 15 Acropora species and 3 other acroporid taxa belonging to the genera Montipora and Astreopora to examine genomic novelties that explain their evolutionary success. We successfully obtained reasonable draft genomes of all 18 species. Molecular dating indicates that the Acropora ancestor survived warm periods without sea ice from the mid or late Cretaceous to the Early Eocene and that diversification of Acropora may have been enhanced by subsequent cooling periods. In general, the scleractinian gene repertoire is highly conserved; however, coral- or cnidarian-specific possible stress response genes are tandemly duplicated in Acropora. Enzymes that cleave dimethlysulfonioproprionate into dimethyl sulfide, which promotes cloud formation and combats greenhouse gasses, are the most duplicated genes in the Acropora ancestor. These may have been acquired by horizontal gene transfer from algal symbionts belonging to the family Symbiodiniaceae, or from coccolithophores, suggesting that although functions of this enzyme in Acropora are unclear, Acropora may have survived warmer marine environments in the past by enhancing cloud formation. In addition, possible antimicrobial peptides and symbiosis-related genes are under positive selection in Acropora, perhaps enabling adaptation to diverse environments. Our results suggest unique Acropora adaptations to ancient, warm marine environments and provide insights into its capacity to adjust to rising seawater temperatures.
Birgus latro (coconut crab) is an edible crustacean that has experienced serious overharvesting throughout its whole habitat range; however, the negative effects of overharvesting on the genetic ...diversity within B. latro populations have not been elucidated. Here, we report sex ratio, body size, and genetic diversity in populations of B. latro in the Ryukyu Islands where large-male-biased overharvesting of B. latro has continued. In 2 of the study populations, the sex ratio was significantly skewed toward females, and in all of the study populations large males were rare, which we attributed to sex- and size-biased overharvesting. We found no differences in genetic diversity between small and large individuals, suggesting that genetic diversity, even among the large (i.e., old) individuals, may have had already been negatively affected by overharvesting. Continued monitoring of sex ratio, body size and genetic diversity are needed for effective management of the study populations.
Elevated sea surface temperature associated with global warming is a serious threat to coral reefs. Elevated temperatures directly or indirectly alter the distribution of coral-pathogen interactions ...and thereby exacerbate infectious coral diseases. The pathogenic bacterium
Vibrio coralliilyticus
is well-known as a causative agent of infectious coral disease. Rising sea surface temperature promotes the infection of corals by this bacterium, which causes several coral pathologies, such as bacterial bleaching, tissue lysis, and white syndrome. However, the effects of thermal stress on coral immune responses to the pathogen are poorly understood. To delineate the effects of thermal stress on coral immunity, we performed transcriptome analysis of aposymbiotic primary polyps of the reef-building coral
Acropora digitifera
exposed to
V. coralliilyticus
under thermal stress conditions.
V. coralliilyticus
infection of coral that was under thermal stress had negative effects on various molecular processes, including suppression of gene expression related to the innate immune response. In response to the pathogen, the coral mounted various responses including changes in protein metabolism, exosome release delivering signal molecules, extracellular matrix remodeling, and mitochondrial metabolism changes. Based on these results, we provide new insights into innate immunity of
A. digitifera
against pathogen infection under thermal stress conditions.
Mussels, which occupy important positions in marine ecosystems, attach tightly to underwater substrates using a proteinaceous holdfast known as the byssus, which is tough, durable, and resistant to ...enzymatic degradation. Although various byssal proteins have been identified, the mechanisms by which it achieves such durability are unknown. Here we report comprehensive identification of genes involved in byssus formation through whole-genome and foot-specific transcriptomic analyses of the green mussel, Perna viridis. Interestingly, proteins encoded by highly expressed genes include proteinase inhibitors and defense proteins, including lysozyme and lectins, in addition to structural proteins and protein modification enzymes that probably catalyze polymerization and insolubilization. This assemblage of structural and protective molecules constitutes a multi-pronged strategy to render the byssus highly resistant to environmental insults.
Sexual reproduction of scleractinians has captured the attention of researchers and the general public for decades. Although extensive ecological data has been acquired, underlying molecular and ...cellular mechanisms remain largely unknown. In this study, to better understand mechanisms underlying gametogenesis, we isolated ovaries and testes at different developmental phases from a gonochoric coral, Euphyllia ancora, and adopted a transcriptomic approach to reveal sex- and phase-specific gene expression profiles. In particular, we explored genes associated with oocyte development and maturation, spermiogenesis, sperm motility / capacitation, and fertilization.
1.6 billion raw reads were obtained from 24 gonadal samples. De novo assembly of trimmed reads, and elimination of contigs derived from symbiotic dinoflagellates (Symbiodiniaceae) and other organisms yielded a reference E. ancora gonadal transcriptome of 35,802 contigs. Analysis of 4 developmental phases identified 2023 genes that were differentially expressed during oogenesis and 678 during spermatogenesis. In premature/mature ovaries, 631 genes were specifically upregulated, with 538 in mature testes. Upregulated genes included those involved in gametogenesis, gamete maturation, sperm motility / capacitation, and fertilization in other metazoans, including humans. Meanwhile, a large number of genes without homology to sequences in the SWISS-PROT database were also observed among upregulated genes in premature / mature ovaries and mature testes.
Our findings show that scleractinian gametogenesis shares many molecular characteristics with that of other metazoans, but it also possesses unique characteristics developed during cnidarian and/or scleractinian evolution. To the best of our knowledge, this study is the first to create a gonadal transcriptome assembly from any scleractinian. This study and associated datasets provide a foundation for future studies regarding gametogenesis and differences between male and female colonies from molecular and cellular perspectives. Furthermore, our transcriptome assembly will be a useful reference for future development of sex-specific and/or stage-specific germ cell markers that can be used in coral aquaculture and ecological studies.
Scleractinian corals of the genus Montipora (Anthozoa, Cnidaria) possess some unusual biological traits, such as vertical transmission of algal symbionts; however, the genetic bases for those traits ...remain unknown. We performed extensive comparative genomic analyses among members of the family Acroporidae (Montipora, Acropora, and Astreopora) to explore genomic novelties that might explain unique biological traits of Montipora using improved genome assemblies and gene predictions for M. cactus, M. efflorescens and Astreopora myriophthalma.
We obtained genomic data for the three species of comparable high quality to other published coral genomes. Comparative genomic analyses revealed that the gene families restricted to Montipora are significantly more numerous than those of Acropora and Astreopora, but their functions are largely unknown. The number of gene families specifically expanded in Montipora was much lower than the number specifically expanded in Acropora. In addition, we found that evolutionary rates of the Montipora-specific gene families were significantly higher than other gene families shared with Acropora and/or Astreopora. Of 40 gene families under positive selection (Ka/Ks ratio > 1) in Montipora, 30 were specifically detected in Montipora-specific gene families. Comparative transcriptomic analysis of early life stages of Montipora, which possesses maternally inherited symbionts, and Acropora, which lacks them, revealed that most gene families continuously expressed in Montipora, but not expressed in Acropora do not have orthologs in Acropora. Among the 30 Montipora-specific gene families under positive selection, 27 are expressed in early life stages.
Lineage-specific gene families were important to establish the genus Montipora, particularly genes expressed throughout early life stages, which under positive selection, gave rise to biological traits unique to Montipora. Our findings highlight evolutionarily acquired genomic bases that may support symbiosis in these stony corals and provide novel insights into mechanisms of coral-algal symbiosis, the physiological foundation of coral reefs.
Prion-like protein propagation is considered a common pathogenic mechanism in neurodegenerative diseases. Here we investigate the in vivo propagation pattern and aggregation state of mutant ...α-synuclein by injecting adeno-associated viral (AAV)-α-synuclein-A53T-EGFP into the mouse olfactory cortex. Comparison of aggregation states in various brain regions at multiple time points after injection using western blot analyses shows that the monomeric state of the mutant/misfolded protein propagates to remote brain regions by 2 weeks and that the propagated proteins aggregate in situ after being incorporated into neurons. Moreover, injection of Alexa 488-labeled α-synuclein-A53T confirms the monomeric propagation at 2 weeks. Super-resolution microscopy shows that both α-synuclein-A53T proteins propagate via the lymphatic system, penetrate perineuronal nets, and reach the surface of neurons. Electron microscopy shows that the propagated mutant/misfolded monomer forms fibrils characteristic of Parkinson’s disease after its incorporation into neurons. These findings suggest a mode of propagation different from that of aggregate-dependent propagation.
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•Prionoid protein propagation is a common mechanism of neurodegenerative diseases•Neuron-to-neuron propagation of aggregated disease proteins has been assumed•We reveal propagation of the monomer disease protein via brain lymphatic system•The brain lymphatic propagation of monomer is a target of future therapeutics
In neurodegenerative disease, prion-like infection of disease protein is suspected. As a route of propagation, neuron-to-neuron propagation of aggregated disease proteins has been assumed thus far. In this study, Fujita et al. describe a pathway for rapidly propagating the monomer state of disease protein via the brain lymphatic system.
Abstract
Reef-building corals and photosynthetic, endosymbiotic algae of the family Symbiodiniaceae establish mutualistic relationships that are fundamental to coral biology, enabling coral reefs to ...support a vast diversity of marine species. Although numerous types of Symbiodiniaceae occur in coral reef environments, Acropora corals select specific types in early life stages. In order to study molecular mechanisms of coral–algal symbioses occurring in nature, we performed whole-genome transcriptomic analyses of Acropora tenuis larvae inoculated with Symbiodinium microadriaticum strains isolated from an Acropora recruit. In order to identify genes specifically involved in symbioses with native symbionts in early life stages, we also investigated transcriptomic responses of Acropora larvae exposed to closely related, nonsymbiotic, and occasionally symbiotic Symbiodinium strains. We found that the number of differentially expressed genes was largest when larvae acquired native symbionts. Repertoires of differentially expressed genes indicated that corals reduced amino acid, sugar, and lipid metabolism, such that metabolic enzymes performing these functions were derived primarily from S. microadriaticum rather than from A. tenuis. Upregulated gene expression of transporters for those metabolites occurred only when coral larvae acquired their natural symbionts, suggesting active utilization of native symbionts by host corals. We also discovered that in Acropora, genes for sugar and amino acid transporters, prosaposin-like, and Notch ligand-like, were upregulated only in response to native symbionts, and included tandemly duplicated genes. Gene duplications in coral genomes may have been essential to establish genomic novelties for coral–algae symbiosis.
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