Biology subjects

Yamashiro, S.

Publications and source records attributed to Yamashiro, S..

4 recordsLinked to original sources

bioRxiv2025

Shear Stress Induces Concentration Gradient Distributions of Membrane Proteins in Live Cells

Cells sense and respond to fluid shear stress. Cell surfaces are exposed to flow, yet the influence of shear stress on the behavior of plasma membrane proteins remains unclear. Here we show that extracellular flow induces the gradient distribution of cell membrane proteins with increasing concentration toward the downstream direction of the flow. Shear stress at 10-30 dynes/cm2 caused formation of concentration gradients of both GPI-anchored proteins and transmembrane proteins, including integrin{beta}1, E-cadherin and the insulin receptor in Xenopus XTC cells. Using single-molecule live-cell imaging, we found that GPI-anchored T-cadherin molecules are dragged along the direction of flow under shear stress. In addition, shear stress induced concentration gradients of membrane proteins in COS-7 cells and human umbilical vein endothelial cells (HUVECs). Our findings suggest that external flow directly transports membrane proteins, establishing concentration gradients that may contribute to the cellular flow-sensing mechanism.

biophysics↗

bioRxiv2024

The heterogeneity of dermal mesenchymal cells reproduced in skin equivalents regulate barrier function and elasticity.

The heterogeneity of dermal mesenchymal cells, including perivascular mesenchymal cells and papillary and reticular fibroblasts, plays critical roles in skin homeostasis. Herein, we present human skin equivalents (HSEs), in which pericytes, papillary fibroblasts, and reticular fibroblasts are spatially organized through autonomous three-cell interactions among epidermal keratinocytes, dermal fibroblasts, and vascular endothelial cells. The replication of dermal mesenchymal cell heterogeneity enhances skin functions, including epithelialization, epidermal barrier formation, and dermal elasticity, enabling in vitro evaluation of drug efficacy using methodologies that are identical to those used in human clinical studies. Furthermore, ascorbic acid-induced epidermal turnover and synthesis of well-aligned extracellular matrix via perivascular niche cells play crucial roles in improving skin barrier function and elasticity. Therefore, HSEs with heterogeneous dermal mesenchymal cells may improve our understanding of the mechanisms underlying skin homeostasis through cell-to-cell communication and serve as a model to animal experiments for developing precision medicine.

bioengineering↗

bioRxiv2021

A mechanism with severing near barbed ends and annealing explains structure and dynamics of dendritic actin networks

Single molecule imaging has shown that part of actin disassembles within a few seconds after incorporation into the dendritic filament network in lamellipodia, suggestive of frequent destabilization near barbed ends. To investigate the mechanisms behind network remodeling, we created a stochastic model with polymerization, depolymerization, branching, capping, uncapping, severing, oligomer diffusion, annealing, and debranching. We find that filament severing, enhanced near barbed ends, can explain the single molecule actin lifetime distribution, if oligomer fragments reanneal to free ends with rate constants comparable to in vitro measurements. The same mechanism leads to actin networks consistent with measured filament, end, and branch concentrations. These networks undergo structural remodeling, leading to longer filaments away from the leading edge, at the +/- 35{degrees} orientation pattern. Imaging of actin speckle lifetimes at sub-second resolution verifies frequent disassembly of newly-assembled actin. We thus propose a unified mechanism that fits a diverse set of basic lamellipodia phenomenology.

cell biology↗

bioRxiv2020

Investigation of fascin1, a marker of mature dendritic cells, reveals a New role for IL-6 signaling in chemotaxis.

Migration of mature dendritic cells (DCs) to lymph nodes is critical for the initiation of adaptive immunity. While CCR7, a a G-protein-coupled receptor for CCL19/21 chemokines, is known to be essential for chemotaxis of mature DCs, the molecular mechanism linking inflammation to chemotaxis remains unclear. We previously demonstrated that fascin1, an actin-bundling protein, increases chemotaxis of mature DCs. In this paper we showed that fascin1 enhanced Interleukin (IL)-6 secretion and signaling. Furthermore, we demonstrated that IL-6 signaling is required for chemotaxis. Blockage of IL-6 signaling in WT DCs with an anti-IL-6 receptor (IL-6R) antibody inhibited chemotaxis toward CCL19. Likewise, knockout (KO) of IL-6R inhibited chemotaxis of BMDCs. The addition of soluble IL-6R and IL-6 rescued chemotaxis of IL-6R KO BMDCs, underscoring the role of IL-6 signaling in chemotaxis. We found that IL-6 signaling is required for internalization of CCR7, the initial step of CCR7 recycling. CCR7 recycling is known to be essential for CCR7-mediated chemotaxis, explaining why IL-6 signaling is needed for chemotaxis of mature DCs. Our results have identified IL-6 signaling as a new regulatory pathway for CCR7/CCL19-mediated chemotaxis, and suggest that rapid migration of mature DCs to lymph nodes depends on inflammation-associated IL-6 signaling.

immunology↗