Biology subjects

Tahara, Y.

Publications and source records attributed to Tahara, Y..

4 recordsLinked to original sources

bioRxiv2026

Reconstitution in a minimal synthetic bacterium reveals distinct Mollicute MreB-based motility systems driven by orthogonal force directions

MreB, a bacterial actin homolog, is widely conserved in bacteria where it functions as a scaffold for a peptidoglycan synthesis. Intriguingly, members of the cell wall-lacking Mollicutes retain multiple mreB genes despite the absence of peptidoglycan. Previous work demonstrated that two MreB isoforms from Spiroplasma can reconstitute swimming motility in the minimal synthetic bacterium syn3B, indicating that MreB was repurposed for motility. Here, we expressed seven MreBs from Haloplasma contractile, an early-diverging Mollicute, in syn3B. Approximately 50% of cells elongated, and 15% exhibited curving and coiling movements that resembled Haloplasma but differed from Spiroplasma motility. Systematic analysis of isoform combinations revealed that movement requires specific MreB pairs, and that additional isoforms enhance motility efficiency. Cryo-electron tomography showed membrane-associated ribbons composed of MreB filaments. Mathematical modeling demonstrated that Haloplasma- and Spiroplasma-type movements can be reproduced by altering only the direction of force generation. Thus, diversification of force orientation within an actin homolog enabled independent evolution of distinct motility systems in Mollicutes.

Synthetic Biology↗

bioRxiv2024

A heterocyclic compound inhibits viral release by inducing cell surface BST2/Tetherin/CD317/HM1.24

The introduction of combined antiretroviral therapy (cART) has greatly improved the quality of life of human immunodeficiency virus type 1 (HIV-1)-infected individuals. Nonetheless, the ever-present desire to seek out a full remedy for HIV-1 infections makes the discovery of novel antiviral medication compelling. Owing to this, a new late-stage inhibitor, Lenacapavir/Sunlenca, an HIV multi-phase suppressor, was clinically authorized in 2022. Besides unveiling cutting-edge antivirals inhibiting late-stage proteins or processes, newer therapeutics targeting host restriction factors hold promise for the curative care of HIV-1 infections. Notwithstanding, bone marrow stromal antigen 2 (BST2)/Tetherin/CD317/HM1.24, which entraps progeny virions is an appealing HIV-1 therapeutic candidate. In this study, a novel drug screening system was established, using the Jurkat/Vpr-HiBiT T cells, to identify drugs that could obstruct HIV-1 release; the candidate compounds were selected from the Ono Pharmaceutical compound library. Jurkat T cells expressing Vpr-HiBiT were infected with NL4-3, and the amount of virus release was quantified indirectly by the amount of Vpr-HiBiT incorporated into the progeny virions. Subsequently, the candidate compounds that suppressed viral release were used to synthesize the heterocyclic compound, HT-7, which reduces HIV-1 release with less cellular toxicity. Notably, HT-7 increased cell surface BST2 coupled with HIV-1 release reduction in Jurkat cells but not Jurkat/KO-BST2 cells. Seemingly, HT-7 impeded simian immunodeficiency virus (SIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) release. Concisely, these results suggest that the reduction in viral release, following HT-7 treatment, resulted from the modulation of cell surface expression of BST2 by HT-7. ImportanceA collection of scientific strategies has been revealed to find long-term cure for HIV-1 infection. One of these techniques, the therapeutic approach, involves harnessing late events that are not targeted by current medication. The regulator of HIV-1 assembly and release, the HIV-1 Gag protein, has emerged as a prospective inhibitor. We set up a high-efficiency, economically viable, and facile screening system for the identification of late-stage inhibitors. Herein, we discovered a heterocyclic compound that inhibits HIV-1 release. This newly high- performance testing technique can be employed in virological research for investigating HIV- 1 late-stage processes.

microbiology↗

bioRxiv2024

In quiescent G0 phase, Schizosaccharomyces pombe Mis4 ensures full nuclear separation during the subsequent M phase

Evolutionarily conserved Mis4 establishes cohesion between replicated sister chromatids in vegetatively proliferating cells. In the fission yeast, Schizosaccharomyces pombe, defects in Mis4 lead to premature separation of sister chromatids, resulting in fatal chromosome mis-segregation during mitosis. In humans, NIPBL, an ortholog of Mis4, is responsible for a severe multisystem disorder called Cornelia de Lange syndrome. We previously reported that Mis4 is also essential in non-proliferating quiescent cells. Whereas wild-type fission yeast cells can maintain high viability for long periods without cell division in the quiescent G0 phase, mis4-450 mutant cells cannot. In this report, we show that Mis4 is not required for cells to enter G0 phase, but is essential to exit from it. When resuming mitosis after passage of G0, mis4 mutant cells segregated sister chromatid successfully, but insufficiently separated daughter nuclei consequently formed dikaryon-like cells. These findings suggest a novel role of Mis4/NIPBL in non-dividing quiescent cells, which is prerequisite for full nuclear separation upon resumed mitosis. As most human cells are in the quiescent state, this study may facilitate development of novel therapies for human diseases caused by Mis4/NIPBL deficiency.

cell biology↗

bioRxiv2021

Reconstitution of Spiroplasma swimming by expressing two bacterial actins in synthetic minimal bacterium

Motility is one of the most important features of life, but its evolutionary origin remains unknown. In this study, we focused on Spiroplasma, commensal, or parasitic bacteria. They swim by switching the helicity of a ribbon-like cytoskeleton that comprises six proteins, each of which evolved from a nucleosidase and bacterial actin called MreB. We expressed these proteins in a synthetic, non-motile minimal bacterium, JCVI-syn3.0B, whose reduced genome was computer-designed and chemically synthesized. The synthetic bacterium exhibited swimming motility with features characteristic of Spiroplasma swimming. Moreover, some combinations of the two proteins produced a helical cell shape and swimming, suggesting that the swimming originated from the differentiation and coupling of bacterial actins, and we also obtained a minimal system for motility of the synthetic bacterium. One-Sentence SummaryThe minimal system comprised two bacterial actins that provided cell helicity and swimming to the synthetic minimal bacterium.

synthetic biology↗