Insecticide resistance in Drosophila melanogaster : genetic basis, fitness costs and compensatory evolution

Resistenties tegen een bestrijdingsmiddel is voor een organisme een 'kostbare' zaak. Het opbouwen, in stand houden en laten functioneren van een dergelijk verdedigingsmecha­nisme kost hem namelijk moeite, tijd en energie. Daarom wordt verwacht dat het vóór­komen van resistentie binnen een populatie afneemt zodra het desbetreffende bestrijdings­middel niet meer wordt gebruikt. Er zijn echter aanwijzingen dat, ook nadat het bestrij­dingsmiddel niet meer wordt gebruikt, resistentie toch in natuurlijke populaties aanwezig kan blijven. Dit wordt mogelijk verklaard door 'compenserende evolutie', dat wil zeggen mutaties die de kosten van resistentie verlagen. Als gevolg hiervan is de ontwikkeling en de handhaving van resistentie een serieus en toenemend probleem voor de plaagbestrijding in de landbouw en in de gezondheidszorg. Het is niet alleen belangrijk om de evolutie en de genetische basis van resistentie te begrijpen, maar ook de dynamiek van compenserende evolutie. Het onderzoek van Renate Geerts was gericht op het ophelderen van de genetische basis van resistentie tegen het bestrijdingsmiddel DDT en om inzicht te verschaffen in het optreden van compenserende evolutie in twee onafhankelijk van elkaar gekweekte fruitvlieg-populaties.

Arginine π-stacking drives binding to fibrils of the Alzheimer protein Tau

Aggregation of the Tau protein into fibrils defines progression of neurodegenerative diseases, including Alzheimer's Disease. The molecular basis for potentially toxic reactions of Tau aggregates is poorly understood. Here we show that π-stacking by Arginine side-chains drives protein binding to Tau fibrils. We mapped an aggregation-dependent interaction pattern of Tau. Fibrils recruit specifically aberrant interactors characterised by intrinsically disordered regions of atypical sequence features. Arginine residues are key to initiate these aberrant interactions. Crucial for scavenging is the guanidinium group of its side chain, not its charge, indicating a key role of π-stacking chemistry for driving aberrant fibril interactions. Remarkably, despite the non-hydrophobic interaction mode, the molecular chaperone Hsp90 can modulate aberrant fibril binding. Together, our data present a molecular mode of action for derailment of protein-protein interaction by neurotoxic fibrils

Arginine π-stacking drives binding to fibrils of the Alzheimer protein Tau

Aggregation of the Tau protein into fibrils defines progression of neurodegenerative diseases, including Alzheimer's Disease. The molecular basis for potentially toxic reactions of Tau aggregates is poorly understood. Here we show that π-stacking by Arginine side-chains drives protein binding to Tau fibrils. We mapped an aggregation-dependent interaction pattern of Tau. Fibrils recruit specifically aberrant interactors characterised by intrinsically disordered regions of atypical sequence features. Arginine residues are key to initiate these aberrant interactions. Crucial for scavenging is the guanidinium group of its side chain, not its charge, indicating a key role of π-stacking chemistry for driving aberrant fibril interactions. Remarkably, despite the non-hydrophobic interaction mode, the molecular chaperone Hsp90 can modulate aberrant fibril binding. Together, our data present a molecular mode of action for derailment of protein-protein interaction by neurotoxic fibrils

Retinyl ester hydrolases and their roles in vitamin A homeostasis☆

In mammals, dietary vitamin A intake is essential for the maintenance of adequate retinoid (vitamin A and metabolites) supply of tissues and organs. Retinoids are taken up from animal or plant sources and subsequently stored in form of hydrophobic, biologically inactive retinyl esters (REs). Accessibility of these REs in the intestine, the circulation, and their mobilization from intracellular lipid droplets depends on the hydrolytic action of RE hydrolases (REHs). In particular, the mobilization of hepatic RE stores requires REHs to maintain steady plasma retinol levels thereby assuring constant vitamin A supply in times of food deprivation or inadequate vitamin A intake. In this review, we focus on the roles of extracellular and intracellular REHs in vitamin A metabolism. Furthermore, we will discuss the tissue-specific function of REHs and highlight major gaps in the understanding of RE catabolism. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism