Biology subjects

Takahashi, I.

Publications and source records attributed to Takahashi, I..

4 recordsLinked to original sources

bioRxiv2025

Impaired store-operated Ca2+ entry in mouse epidermis leads to reduced epidermal barrier function via Klk activation.

Store-operated Ca2+ entry (SOCE) is a mechanism by which STIM1/2 detect calcium depletion in the endoplasmic reticulum (ER) and activate ORAI1/TRPC channels on the cell membrane to induce calcium influx into the cytoplasm. This study aimed to investigate SOCEs role in the skin epidermis in vivo, using female mice with epithelial tissue-specific Stim1 and Stim2 knockout (Stim1/2 cKO) and control mice (Stim1/2fl/fl). Keratinocytes from Stim1/2 cKO mice exhibited reduced Stim1 and Stim2 gene expression levels and impaired SOCE function compared with the controls. Histological analysis revealed hyperkeratosis in the Stim1/2 cKO tissues; however, no significant changes were observed in the proliferation or migration of keratinocytes or wound healing of the back skin. RNA-seq analysis indicated altered keratinization and cell-to-cell adhesion in the Stim1/2 cKO mice. Additionally, transepidermal water loss (TEWL) was increased significantly, and a biotinylated reagent diffused from the subcutaneous area into the granular layer, signifying compromised barrier function in the Stim1/2 cKO mice. The Stim1/2 cKO mice exhibited alterations in desmoglein 1 (Dsg1) and elevated levels of Kallikrein-related peptidase (Klk) 6 and Klk7, leading to increased trypsin- and chymotrypsin-like serine protease activities, respectively. These results suggest that SOCE dysfunction leads to hyperkeratosis and impaired epidermal barrier function via Klk activation without affecting skin cell proliferation in vivo. These novel findings improve understanding of the molecular mechanisms underlying calcium signaling in the epidermis barrier and suggest potential avenues for investigating related skin pathologies linked to calcium homeostasis, such as Hailey-Hailey disease (HHD) and Darier disease (DD).

cell biology↗

bioRxiv2022

Deep embedded clustering by relevant scales and genome-wide association study in autism

The etiology of autism spectrum disorders (ASD) remains unclear. Stratifying patients with ASD may help to identify genetically homogeneous subgroups. Using a deep embedded clustering algorithm, we conducted cluster analyses of Simons Foundation Powering Autism Research for Knowledge (SPARK) datasets and performed genome-wide association studies (GWAS) of the clusters. We observed no significant associations in the conventional GWAS comparing all patients to all controls. However, in the GWAS, comparing patients divided into clusters with similar phenotypes to controls (cluster-based GWAS), we identified 90 chromosomal loci that satisfied the P < 5.0 x 10-8, several of which were located within or near previously reported candidate genes for ASD. Our findings suggest that clustering may successfully identify subgroups with relatively homogeneous disease etiologies.

genomics↗

bioRxiv2022

Canonical Strigolactones Are Not the Tillering-Inhibitory Hormone but Rhizospheric Signals in Rice

The plant hormones strigolactones (SLs) regulate shoot branching and mediate the communication with symbiotic mycorrhizal fungi, but also with noxious root parasitic weeds, such as Striga spp. SLs derive from carlactone (CL) and are divided structurally into canonical and non-canonical SLs. However, the questions about particular biological functions of the two groups and the identification of the SL that inhibits shoot branching are still unanswered, hampering targeted modification of SL pattern towards improving plant architecture and resistance against Striga. Here, we reported that 4-deoxyorobanchol (4DO) and orobanchol, the two canonical SLs in rice, do not have major role in determining rice shoot architecture. CRISPR/Cas9 mediated Osmax1-900 mutants, lacking these two SLs, do not show the high tillering and dwarf phenotype typical for SL-deficient plants. However, the absence of 4DO and orobanchol in root exudates significantly decreased their capability in inducing Striga seed germination, while caused only a delay in root colonization by mycorrhizal fungi. To confirm the genetic evidence, we used the SL-biosynthesis inhibitor TIS108. Our results showed that TIS108 is a MAX1-specific inhibitor that lowers 4DO and orobanchol synthesis, conferring a resistance to Striga without a severe impact on rice architecture. Hence, our work uncovers the specific function of canonical SLs as rhizospheric signals and paves the way for establishing chemical and genetic based approaches for combating the root parasitic weeds, by targeted depletion of their release.

plant biology↗

bioRxiv2018

Triazole ureas covalently bind to strigolactone receptors and regulate signaling

Strigolactones (SLs), a class of plant hormones with multiple functions, mediate plant-plant and plant-microorganism communications in the rhizosphere. In this study, we developed potent strigolactone antagonists, which covalently bind to the strigolactone receptor D14, by preparing an array of triazole urea compounds. Using yeast two-hybrid assays and rice tillering assays, we identified a triazole urea compound KK094 as a potent inhibitor of strigolactone receptors. The LC-MS/MS analysis and X-ray crystallography concluded that KK094 was hydrolyzed by D14, and that a reaction product of this degradation covalently binds to the Ser residue of the catalytic triad of D14. We also identified KK052 and KK073, whose effects on D14-D53/D14-SLR1 complex formation were opposite due to a trifluoromethyl group on its benzene ring. These results demonstrate that triazole urea compounds are potentially powerful tools for agricultural application and may be useful for the elucidation of the complicated mechanism underlying SL-perception.

plant biology↗