Biology subjects

Yoshioka, D.

Publications and source records attributed to Yoshioka, D..

3 recordsLinked to original sources

bioRxiv2026

Asymmetric turnover dynamics of Nav1.6 voltage-gated sodium channels at the axon initial segment

Nav1.6 voltage-gated sodium channels are critical for shaping action potentials, and their precise localization at the axon initial segment (AIS) is essential for neuronal excitability. However, the turnover mechanisms that maintain this spatial pattern remain unclear. Here, we present a genetically engineered mouse in which endogenous Nav1.6 carries a Cre-switchable fluorescent tag, enabling us to simultaneously trace the turnover of pre-existing and newly synthesized Nav1.6 without perturbing AIS structure. Using this system, we determine the physiological lifetimes of Nav1.6 at the AIS in vivo and in vitro, and further uncover the spatially asymmetric turnover dynamics, with the proximal and distal AIS organizing a source-to-sink gradient. Based on the quantified parameters, computational modeling clarifies that this asymmetry promotes efficient clearance of older molecules, thereby supporting AIS quality control. Collectively, these findings provide a technical and conceptual foundation for understanding how molecular turnover contributes to AIS homeostasis.

neuroscience↗

bioRxiv2025

Computed Tomography-Derived Elastic Modulus as a Noninvasive Marker of Aortic Wall Integrity: Correlation with Histopathology in the Ascending Aorta

BackgroundAscending aortic aneurysms and dissections are life-threatening conditions often requiring prophylactic surgeries. Current guidelines rely primarily on aortic diameter for intervention; however, many dissections occur without severe dilation. Mechanical properties, such as elastic modulus have emerged as potential predictors of disease progression; nonetheless, noninvasive clinical applications remain limited. This study evaluated the relationship between the computed tomography (CT)-derived elastic modulus of the ascending aorta and the histopathological characteristics of the aortic media. MethodsThirty patients who underwent surgical ascending aorta replacement were included in this study. Preoperative CT was used to calculate the aortic elastic modulus based on geometric measurements and pulse pressure. Resected aortic specimens were subjected to histological and immunohistochemical analyses to assess elastin, collagen, vascular smooth muscle cells (VSMCs), and smoothelin expression. Correlation analyses between the CT-derived elastic modulus and aortic media composition were conducted after adjusting for age and aortic diameter. ResultsThe CT-derived elastic modulus exhibited a significant negative correlation with elastin area and a positive correlation with collagen area. Additionally, a moderate negative correlation was observed between the elastic modulus and elastin fiber waviness. A strong negative correlation was detected between the elastic modulus and the proportion of contractile-type (smoothelin-positive) VSMCs. These findings remained significant after adjusting for confounders. ConclusionsCT-derived elastic modulus of the ascending aorta reflects the underlying pathological changes, including extracellular matrix remodeling and VSMC phenotypic modulation. Noninvasive assessment of aortic mechanical properties may provide novel insights into aortic disease progression and therapeutic responses.

pathology↗

bioRxiv2024

Coupling Between Functionality and Trafficking to the Axon Initial Segment in KCNQ2/3 K+ Channels

KCNQ2/3 are the predominant voltage-gated K+ channels localized at the axon initial segment (AIS), the critical site for the initiation of action potentials and the plasticity of excitability. Both the functionality and spatial distribution of KCNQ2/3 provide the basis for the regulation of neuronal excitability and the pathogenesis of various neurological disorders, including epilepsy. However, less is known about how functionality is coupled with trafficking regulation in KCNQ2/3. Here, we study the AIS localization of KCNQ2/3 by performing both multiple- and single-molecule imaging analyses. We found that low-activity mutations in the KCNQ3 subunit affect all of the 3D dynamics composed of lateral diffusion and exo/endocytosis processes through disruption of interaction with ankyrin-G, consequently suppressing the AIS targeting of KCNQ2/3. Thus, the functionality of KCNQ2/3 is coupled with its trafficking regulation, enhancing our understanding of the mechanisms underlying physiological and pathophysiological changes in neuronal excitability.

neuroscience↗