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Avidity-driven polarity establishment via multivalent lipid-GTPase module interactions
The EMBO journal, 2019, 38,
While Rho GTPases are indispensible regulators of cellular polarity, the mechanisms underlying their anisotropic activation at membranes have been elusive. Using the budding yeast Cdc42 GTPase module, which includes a guanine nucleotide exchange factor (GEF) Cdc24 and the scaffold Bem1, we find that avidity generated via multivalent anionic lipid interactions is a critical mechanistic constituent of polarity establishment. We identify basic cluster (BC) motifs in Bem1 that drive the interaction of the scaffold-GEF complex with anionic lipids at the cell pole. This interaction appears to influence lipid acyl chain ordering, thus regulating membrane rigidity and feedback between Cdc42 and the membrane environment. Sequential mutation of the Bem1 BC motifs, PX domain, and the PH domain of Cdc24 lead to a progressive loss of cellular polarity stemming from defective Cdc42 nanoclustering on the plasma membrane and perturbed signaling. Our work demonstrates the importance of avidity via multivalent anionic lipid interactions in the spatial control of GTPase activation.
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Molecular mechanisms for the destabilization of model membranes by islet amyloid polypeptide
Biophysical chemistry, 2019, 245, 34-40
Misfolding of human islet amyloid polypeptide (hIAPP) into insoluble aggregates is associated with Type 2 diabetes. It has been suggested that hIAPP toxicity may be due to its accumulation in pancreatic islets, causing membrane disruption and cell permeabilization, however the molecular basis underlying its lipid association are still unclear. Here, we combine solid-state NMR, fluorescence and bright field microscopy to investigate hIAPP - lipid membrane interactions. Real-time microscopy highlights a time-dependent penetration of hIAPP oligomers toward the most buried layers of the lipid vesicles until the membrane disrupts. Deuterium NMR was conducted on liposomes at different hIAPP concentration to probe lipid internal order and thermotropism. The gel-to-fluid phase transition of the lipids is decreased by the presence of hIAPP, and site-specific analysis of the order parameter showed a significant increase of lipid order for the first eight positions of the acyl chain, suggesting a partial insertion of the peptide inside the bilayer. These results offer experimental insight into the membrane destabilization of hIAPP on model membrane vesicles.
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GRELARD, Axelle; DUFOURC, Erick;
Heat-Triggered Crystallization of Liquid Crystalline Macrocycles Allowing for Conductance Switching through Hysteretic Thermal Phase Transitions
Chemistry-an Asian Journal, 2019, 14, 141-148
A polymesomorphic thermal phase-transition of a macrocyclic amphiphile consisting of aromatic groups and oligoethylene glycol (OEG) chains is reported. The macrocyclic amphiphile exists in a highly-ordered liquid crystal (LC) phase at room temperature. Upon heating, this macrocycle shows phase-transition from columnar-lamellar to nematic LC phases followed by crystallization before melting. Spectroscopic studies suggest that the thermally induced crystallization is triggered by a conformational change at the OEG chains. Interestingly, while the macrocycle returns to the columnar-lamellar phase after cooling from the isotropic liquid, it retains the crystallinity after cooling from the thermally-induced crystal. Thanks to this bistability, conductance switching was successfully demonstrated. A different macrocyclic amphiphile also shows an analogous phase-transition behavior, suggesting that this molecular design is universal for developing switchable and memorizable materials, by means of hysteretic phase-transition processes.
Antoine Loquet Group Accueil Colloids for Health & Nutrition Mentions légales Group History Members Publications Highlights Lipids in all their states Membrane Proteins & Killer Peptides NMR of Soft Matter Contact NMR of Molecular Assemblies Lectures
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