Biology subjects

Geisler, R.

Publications and source records attributed to Geisler, R..

3 recordsLinked to original sources

bioRxiv2023

Dual mechanical impact of β-escin on model lipid membranes

Using artificially reconstituted membranes based on structurally liquidlike phospholipids, we have performed an experimental study on the mechanical impact of the saponin {beta}-aescin, aka escin, a natural biosurfactant extracted from the seeds of the horse chestnut tree Aesculus hippocastanum. The paper focusses on the modulable interaction of escin with DMPC in model membranes in the form of bilayer vesicles and Langmuir monolayers. As regarding to their dual mechanical membrane behavior being both soft solids and viscoelastic fluids, we have outlined the principal energetic and kinetic features describing the insertion of escin as transversally adsorbed or longitudinally integrated within the model membranes. At connection with the structural phase behavior assessed by dedicated microscopies of surface fluorescence and Brewster angle reflectivity, these hybrid escin / phospholipid membranes have been revealed to possess dual mechanical properties connected to their structural rigidness and fluidity behaving both in one way and another. In particular, we observe a soft glassy rheology typical for liquid-crystalline ordered phases at low temperature, which turns into a fluidlike viscoelasticity characteristic of the disordered phases at high physiological temperature. These original results have been discussed in a physicochemical perspective that may pave new avenues of material engineering and / or pharmacological design exploiting the dual mechanical impact of escin as a mechanical modulator of the cellular membrane.

biophysics↗

bioRxiv2018

Abrogation of Stem Loop Binding Protein (Slbp) function leads to a failure of cells to transition from proliferation to differentiation, retinal coloboma and midline axon guidance deficits.

Through forward genetic screening for mutations affecting visual system development, we identified prominent coloboma and cell-autonomous retinal neuron differentiation, lamination and retinal axon projection defects in eisspalte (ele) mutant zebrafish. Additional axonal deficits were present, most notably at midline axon commissures. Genetic mapping and cloning of the ele mutation showed that the affected gene is slbp, which encodes a conserved RNA stem-loop binding protein involved in replication dependent histone mRNA metabolism. Cells throughout the central nervous system remained in the cell cycle in ele mutant embryos at stages when, and locations where, post-mitotic cells have differentiated in wild-type siblings. Indeed, RNAseq analysis showed down-regulation of many genes associated with neuronal differentiation. This was coincident with changes in the levels and spatial localisation of expression of various genes implicated, for instance, in axon guidance, that likely underlie specific ele phenotypes. These results suggest that many of the cell and tissue specific phenotypes in ele mutant embryos are secondary to altered expression of modules of developmental regulatory genes that characterise, or promote transitions in, cell state and require the correct function of Slbp-dependent histone and chromatin regulatory genes.\n\nAuthor SummaryCongenital deficits of eye formation are common in humans and to help understand the genetic basic of such conditions, we are studying zebrafish with comparable eye defects. We identified defects in both the shaping of the eye and in its connections to the brain in eisspalte mutant fish. Further analyses revealed additional deficits in the brain, most notably a severe reduction in neurons and their connections. We find that this is due to an inability of the cells that generate neurons to transition from proliferation to neuronal differentiation. By using a sequencing approach to compare mutant embryos to their normal siblings, we identified the affected gene as slbp, which encodes a protein that binds the mRNAs of other genes important for cell proliferation. This sequencing approach revealed the full extent of changes in gene expression in the mutant, helping us to better understand why the nervous system defects occur. Our study suggests that in the absence of Slbp function, cells lose the ability to transition from the proliferative to the differentiated state and this leads to additional defects in the eyes and brain.

genetics↗

bioRxiv2017

The Calcineurin-FoxO-MuRF1 Signaling Pathway Regulates Myofibril Integrity in Cardiomyocytes

Altered Ca2+ handling is often present in diseased hearts undergoing structural remodeling and functional deterioration. The influences of Ca2+ signaling on cardiac function have been examined extensively, but whether Ca2+ directly regulates sarcomere structure has remained elusive. Using a mutant zebrafish model lacking NCX1 activity in the heart, we explored the impacts of impaired Ca2+ homeostasis on myofibril integrity. Gene expression profiling analysis revealed that the E3 ubiquitin ligase MuRF1 is upregulated in ncx1-deficient hearts. Intriguingly, knocking down MuRF1 activity or inhibiting proteasome activity preserved myofibril integrity in ncx1 deficient hearts, revealing a MuRF1-mediated proteasome degradation mechanism that is activated in response to abnormal Ca2+ homeostasis. Furthermore, we detected an accumulation of the MuRF1 regulator FoxO in the nuclei of ncx1-deficient cardiomyocytes. Overexpression of FoxO in wild type cardiomyocytes induced MuRF1 expression and caused myofibril disarray, whereas inhibiting Calcineurin activity attenuated FoxO-mediated MuRF1 expression and protected sarcomeres from degradation in ncx1-deficient hearts. Together, our findings reveal a novel mechanism by which Ca2+ overload disrupts the myofibril integrity in heart muscle cells by activating a Calcineurin-FoxO-MuRF1-proteosome signaling pathway.

cell biology↗