Biology subjects

Yura, K.

Publications and source records attributed to Yura, K..

5 recordsLinked to original sources

bioRxiv2022

ADAMTS2 regulates radial neuronal migration by activating TGF-β signaling at the subplate layer of the developing neocortex

During the development of the mammalian brain, neocortical structures are formed by the sequential radial migration of newborn excitatory neurons. The early migrating neurons exhibit a multipolar shape, but they undergo a multipolar-to-bipolar transition at the subplate (SP) layer, where extracellular matrix (ECM) components are abundantly expressed. In this study, we revealed that the TGF-{beta} signaling-related ECM proteins, such as latent TGF-{beta}-binding protein 1 (LTBP1) and fibrillin 2, and TGF-{beta} receptor II (TGF-{beta}RII) and its downstream effector, p-smad2/3, are selectively expressed at the SP layer, suggesting that TGF-{beta} is sequestered in a latent form by forming complexes with these ECM components and then its signaling is activated by ECM remodeling. We found that the migrating multipolar neurons transiently express a disintegrin and metalloproteinase with thrombospondin motif 2 (ADAMTS2), an ECM metalloproteinase, just below the SP layer. Knockdown and knockout of Adamts2 suppressed the multipolar-to-bipolar transition of migrating neurons, and therefore, disturbed radial migration. Similar phenotypes were observed by the perturbation of TGF-{beta} signaling in the migrating neurons. Time-lapse luminescence imaging of TGF-{beta} signaling indicated that ADAMTS2 activates this signaling pathway in the migrating neurons during the multipolar-to-bipolar transition at the SP layer. These results suggest that the ADAMTS2 secreted by the migrating multipolar neurons activates TGF-{beta} signaling by ECM remodeling of the SP layer, leading to the multipolar-to-bipolar transition. We propose that the SP layer plays an essential role in the radial neuronal migration as a signaling center of the developing neocortex. SIGNIFICANCEThe neocortex is formed by the sequential radial migration of newborn neurons, which undergo a multipolar-to-bipolar transition at the subplate (SP) layer. The extracellular matrix (ECM) is abundantly expressed in the SP layer. However, the roles of the ECM in the SP layer have been unclear. We found that migrating neurons transiently express a disintegrin and a metalloproteinase with thrombospondin motif 2 (ADAMTS2), an ECM metalloproteinase, just below the SP layer. We show that ADAMTS2 secreted by multipolar migrating neurons activates TGF-{beta} signaling through remodeling of the ECM in the SP layer, leading to the multipolar-to-bipolar transition. Thus, the SP layer plays an essential role in radial migration as a signaling center of the developing neocortex

neuroscience↗

bioRxiv2022

Targeted single-cell genomics reveals novel host adaptation strategies of the symbiotic bacteria Endozoicomonas in Acropora tenuis coral

Endozoicomonas bacteria symbiose with various marine organisms and are known to be beneficial for coral health. However, genome analysis of coral-associated Endozoicomonas has been limited owing to the difficulty in cultivation and metagenomic approach by contamination of host-derived sequences. In this study, we applied a novel single-cell genomics technique using droplet microfluidics to obtain single-cell amplified genome (SAGs) for coral-associated Endozoicomonas spp. genome. We obtained seven novel Endozoicomonas genomes from Acropora tenuis coral. These genomes revealed that Endozoicomonas bacteria played host-associated functions in host corals and had undergone independent host-adaptive evolution in different clades. These adaptive evolutions were mediated by host-derived eukaryotic-like genes, some of which were speculated to influence host immune mechanisms. These genes are speculated to enhance coral tolerance to environmental stresses. This study suggests the possibility of host adaptation of Endozoicomonas spp. in symbiosis with corals and their contribution to coral bleaching tolerance.

microbiology↗

bioRxiv2021

Multi-omics analysis reveals cross-organism interactions in coral holobiont

Corals create an ecosystem, called a holobiont, with intracellular algae (zooxanthellae) and resident bacteria. Zooxanthellae and some bacteria play major roles in the physiological properties of the coral host. However, because of the difficulties in experimental verification of cross-organism interactions, the mechanisms underpinning these interactions are largely unknown. To address this, we here generated and then analyzed multi-omics datasets for corals, zooxanthellae, and bacteria collected at Okinawa, Japan, from November 2014 to September 2016. Using cross-organism co-expression analysis, we successfully characterized the host-alga relationship in the coral holobiont. Specifically, we observed that the coral host dominates the zooxanthellae. The multi-omics analysis also suggested that infection with coral-associated bacteria Endozoicomonas likely involves coral-like ephrin ligands, triggering an immune response of the coral host. This study highlights the potential of the multi-omics approach to elucidate coral-microbe interactions.

systems biology↗

bioRxiv2021

Single-cell metabolite detection and genomics reveals uncultivated talented producer

The production of bioactive metabolites is increasingly recognized as an important function of host-associated bacteria. An example is defensive symbiosis that might account for much of the chemical richness of marine invertebrates including sponges (Porifera), one of the oldest metazoans. However, as most complex microbiomes remain largely uncultivated and lack reference genomes, unequivocally linking metabolic functions to a cellular source is a challenge. Here we report an analysis pipeline of microfluidic encapsulation, Raman microscopy, and integrated digital genomics (MERMAID) for an efficient identification of uncultivated producers. We applied this method to the chemically rich bacteriosponge Theonella swinhoei, previously shown to contain Entotheonella symbionts providing most of its bioactive substances except for the antifungal aurantosides that lacked biosynthetic gene candidates in the metagenome. Raman-guided single-bacterial analysis and sequencing revealed a cryptic, distinct multiproducer, Candidatus Poriflexus aureus from a new Chloroflexi lineage. Its exceptionally large genome contains numerous biosynthetic loci and suggested an even higher chemical richness of this sponge than previously appreciated. This study highlights the importance of complementary technologies to uncover microbiome functions, reveals remarkable parallels between distantly related symbionts of the same host, and adds functional support for diverse chemically prolific lineages being present in microbial dark matter. Significance StatementThe production of bioactive metabolites is increasingly recognized as an important function of host-associated bacteria. However, the acquisition of integrated genomic and metabolic data from uncultivated environmental bacteria is still challenging. In this work, we explored the combination of Raman microscopy and single-cell sequencing to localize chemical features to a specific bacterium in an uncultivated microbiome, and we specified the bacteria in the uncultured lineage as a producer of aurantoside, an antifungal natural product, from a chemically and microbially complex sponge. This study offers a new methodology as well as insights into chemical functions of uncultivated life.

microbiology↗

bioRxiv2020

Exploration of natural red-shifted rhodopsins using a machine learning-based Bayesian experimental design

Microbial rhodopsins are photoreceptive membrane proteins utilized as molecular tools in optogenetics. In this paper, a machine learning (ML)-based model was constructed to approximate the relationship between amino acid sequences and absorption wavelengths using ~800 rhodopsins with known absorption wavelengths. This ML-based model was specifically designed for screening rhodopsins that are red-shifted from representative rhodopsins in the same subfamily. Among 5,558 candidate rhodopsins suggested by a protein BLAST search of several protein databases, 40 were selected by the ML-based model. The wavelengths of these 40 selected candidates were experimentally investigated, and 32 (80%) showed red-shift gains. In addition, four showed red-shift gains > 20 nm, and two were found to have desirable ion-transporting properties, indicating that they were potentially useful in optogenetics. These findings suggest that an ML-based model can reduce the cost for exploring new functional proteins.

biochemistry↗