Biology subjects

Saito, N.

Publications and source records attributed to Saito, N..

22 records · Page 2Linked to original sources

bioRxiv2020

Micro-topographical guidance of macropinocytic signaling patches

In fast moving cells such as amoeba and immune cells, spatio-temporal regulation of dendritic actin filaments shapes large-scale plasma membrane protrusions. Despite the importance in migration as well as in particle and liquid ingestion, how these processes are affected by the micrometer-scale surface features is poorly understood. Here, through quantitative imaging analysis of Dictyostelium on micro-fabricated surfaces, we show that there is a distinct mode of topographically guided cell migration phagotaxis directed by the macropinocytic Ras/PI3K signaling patches. The topography guidance was PI3K-dependent and involved nucleation of a patch at the convex curved surface and confinement at the concave surface. Due to the topography-dependence, constitutive cup formation for liquid uptake in the axenic strain is also destined to trace large surface features. Given the fact that PI3K-dependency of phagocytosis are restricted to large particles in both Dictyostelium and immune cells, topography-dependency and the dual-use of membrane cups may be wide-spread.

biophysics↗

bioRxiv2020

Three-dimensional morphodynamics simulations of macropinocytic cups

*Macropinocytosis is non-specific uptake of the extracellular fluid playing ubiquitous roles in cell growth, immune-surveillance as well as virus entry. Despite its widespread occurrence, it remains unclear how its initial cup-shaped plasma membrane extensions forms without external physical support as in phagocytosis or curvature inducing proteins as in clathrin-mediated endocytosis. Here, by developing a novel computational framework that describes the coupling between bistable reaction-diffusion processes of active signaling patches and membrane deformation, we demonstrate that protrusive force localized to the edge of the patches can give rise to the self-enclosing cup structure without further assumption of local bending or contraction. Efficient uptake requires an appropriate balance between the patch size and the magnitude of protrusive force relative to the cortical tension. Furthermore, our model exhibits a variety of known morphology dynamics including cyclic cup formation, coexistence and competition between multiple cups and cup splitting indicating that these complex morphologies self-organize through mutually dependent dynamics between the reaction-diffusion process and membrane deformation.

biophysics↗

bioRxiv2018

Rac-dependent signaling from keratinocytes promotes differentiation of intradermal white adipocytes

Rac signaling affects numerous downstream targets; however, few studies have established in vivo levels. We generated mice with a single knockout (KO) of Rac1 (Keratin5 (K5)-Cre;Rac1flox/flox, Rac1-KO) and double KO of Rac1 and Rac3 (K5-Cre;Rac1flox/flox;Rac3-/-, Rac1/Rac3-DKO) in keratinocytes. Strikingly, Rac1-KO mice exhibited thinner dermal white adipose tissue, which was considerably further reduced in Rac1/Rac3-DKO mice. DNA microarray using primary keratinocytes from Rac1/Rac3-DKO mice exhibited decreased mRNA levels of Bmp2, Bmp5, Fgf20, Fgf21, Fgfbp1, and Pdgf. Combinational treatment with BMP2 and FGF21 or BMP2 and FGF20 in culture medium, but not individual purified recombinant proteins, could differentiate 3T3-L1 fibroblasts into adipocytes, as could culture media obtained from primary keratinocytes. Conversely, addition of anti-BMP2 or anti-FGF21 antibodies into the culture medium inhibited fibroblast differentiation. Furthermore, combinational treatment with BMP2 and FGF21 promoted adipocyte differentiation only of rat primary white, but not brown, adipocyte precursors. Notably, brown adipogenesis by FGF21 was inhibited by BMP2. Thus, we proposed novel paracrine pathways from keratinocytes to intradermal pre-adipocytes, which function as Rac-dependent modulators of white adipogenesis, but also brown adipogenesis.

cell biology↗

bioRxiv2018

Cytokine profile in human olfactory cleft mucus and associated changes in olfactory function

Multiple factors, including physical changes of the nasal mucosa and epithelium and exposure to air-borne environmental agents, appear to contribute to age-related olfactory loss. However, the molecular aspects of aging-associated olfactory loss in humans are not well understood. Although inflammation can be a significant underlying cause for olfactory impairment, whether aging increases the levels of inflammatory cytokines in the human olfactory mucosa and whether any inflammatory markers are associated with age-related olfactory loss remain unclear. Using a noninvasive method for collecting human olfactory mucus, we characterized and compared inflammatory cytokines, chemokines, and some growth factors, in the mucus collected from the olfactory cleft or the anterior nasal cavity from 12 healthy, young (18-40 years old) and 12 elderly (60-85 years old) individuals. We also hoped to identify candidate molecular biomarkers associated with age-associated olfactory loss in humans. Olfactory thresholds were obtained for two odorants and individual mucus samples were analyzed using multiplex assays for the levels of 30 cytokines. Results indicated elevated levels of certain inflammatory cytokines (IL-12, MCP-1) in olfactory mucus of the elderly, and high levels of some inflammatory factors (MCP-1, IL-8, IL-13 and VEGF) were associated with reduced olfactory sensitivity, suggesting that inflammation may play a role in olfactory decline associated with aging.

neuroscience↗