Biology subjects

Fujisaki, H.

Publications and source records attributed to Fujisaki, H..

4 recordsLinked to original sources

bioRxiv2026

Evolutionary trajectories of teleost olfactory signaling genes shaped by long-term redundancy after whole-genome duplication

Whole-genome duplication (WGD) is a major evolutionary event that drives molecular and species diversification. However, few studies have traced how WGD has shaped the long-term functional evolution of individual genes. Here, we investigated the olfactory marker protein (omp) genes duplicated by the teleost-specific WGD ([~]300 million years ago) through phylogenetic, syntenic, expression, and promoter analyses. Our results suggest that the duplicated omp gene pair has retained redundancy over an extended evolutionary period, leading to both non- and sub-functionalization, thereby generating molecular diversity. Moreover, evolutionary analyses of the olfactory signal transduction cascade revealed prolonged redundancy across its components, likely constrained by gene dosage balance. These findings imply that WGD may have introduced unexpected diversity into the entire olfactory signaling machinery of teleosts through dosage-constrained functional divergence. HighlightsO_LITeleost-specific WGD generated duplicated omp genes that persisted for [~]300 million years. C_LIO_LIExtended redundancy in ompa/ompb led to both non- and sub-functionalization. C_LIO_LIOlfactory transduction genes also show long-term redundancy shaped by dosage constraints. C_LIO_LIWGD likely introduced diversification into teleost olfactory signaling via dosage constraints. C_LI

evolutionary biology↗

bioRxiv2021

Bi-phasic effect of gelatin in myogenesis and skeletal muscle regeneration

Skeletal muscle regeneration requires extracellular matrix (ECM) remodeling including an acute and transient breakdown of collagen that produces gelatin. However, the physiological function of such a remodeling process on muscle tissue repair is unclear. Here we elaborate on a bi-phasic effect of gelatin in skeletal muscle regeneration, mediated by hormetic effects of reactive oxygen species (ROS). Low-dose gelatin stimulates ROS production from NADPH oxidase 2 (NOX2) and simultaneously upregulates antioxidant system for cellular defense, reminiscent of the adaptive compensatory process during mild stress. This response triggers the release of myokine IL-6 which stimulates myogenesis and facilitates muscle regeneration. By contrast, high-dose gelatin stimulates ROS overproduction from NOX2 and mitochondrial chain complex, and ROS accumulation by suppressing antioxidant system, triggering release of TNF, which inhibits myogenesis and regeneration. Our findings reveal gelatin-ROS-IL-6/TNF signaling cascades underlying a hormetic response of myogenic cells to gelatin.

physiology↗

bioRxiv2020

Adhesion to type I collagen fibrous gels induces E- to N- cadherin switching without other EMT-related phenotypes in lung carcinoma cell A549

In culture system, environmental factors, such as increasing exogenous growth factors and adhesion to type I collagen (Col-I) induce epithelial-to-mesenchymal transition (EMT) in cells. Col-I molecules maintain a non-fibril form under acidic conditions, and they reassemble into fibrils under physiological conditions. Col-I fibrils often assemble to form three-dimensional gels. The gels and non-gel-form of Col-I can be utilized as culture substrates and different gel-forming state often elicit different cell behaviors. However, gel-form dependent effects on cell behaviors, including EMT induction, remain unclear. EMT induction in lung cancer cell line A549 has been reported via adhesion to Col-I but the effects of gel form dependency are unelucidated. This study investigated the changes in EMT-related behaviors in A549 cells cultured on Col-I gels. We examined cell morphology, proliferation, single-cell migration and expression of EMT-related features in A549 cells cultured on gels or non-gel form of Col-I and non-treated dish with or without transforming growth factor (TGF)-{beta}1. On Col-I gels, some cells kept cell-cell contacts and formed clusters, others maintained single-cell form. In cell-cell contact regions, E-cadherin expression was downregulated, whereas that of N-cadherin was upregulated. Vimentin and integrins 2 and {beta}1 expression were not increased. In TGF-{beta}1-treated A549 cells, cadherin switched from E- to N-cadherin. Their morphology changed to a mesenchymal form and cells scattered with no cluster formation. Vimentin, integrins 2 and {beta}1 expression were upregulated. Thus, we concluded that culture on Col-I fibrous gels induced E- to N-cadherin switching without other EMT-related phenotypes in A549 cells.

cell biology↗

bioRxiv2017

Energetics and Conformational Pathways of Functional Rotation in the Multidrug Transporter AcrB

The multidrug transporter AcrB transports a broad range of drugs out of the cell by means of the proton-motive force. The asymmetric crystal structure of trimeric AcrB suggests a functionally rotating mechanism for drug transport. Despite various supportive evidences from biochemical and simulation studies for this mechanism, the link between the functional rotation and proton translocation across the membrane remains elusive. Here, calculating the minimum free energy pathway of the functional rotation for the complete AcrB trimer, we describe the structural and energetic basis behind the coupling between the functional rotation and the proton translocation at atomic-level. Free energy calculations show that protonation of Asp408 in the transmembrane portion of the drug-bound protomer drives the functional rotation. The conformational pathway identifies vertical shear motions among several transmembrane helices, which regulates alternate access of water in the transmembrane as well as peristaltic motions pumping drugs in the periplasm.

biophysics↗