TRAF4 Is a Novel Phosphoinositide-Binding Protein Modulating Tight Junctions and Favoring Cell Migration

Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) is frequently overexpressed in carcinomas, suggesting a specific role in cancer. Although TRAF4 protein is predominantly found at tight junctions (TJs) in normal mammary epithelial cells (MECs), it accumulates in the cytoplasm of malignant MECs. How TRAF4 is recruited and functions at TJs is unclear. Here we show that TRAF4 possesses a novel phosphoinositide (PIP)-binding domain crucial for its recruitment to TJs. Of interest, this property is shared by the other members of the TRAF protein family. Indeed, the TRAF domain of all TRAF proteins (TRAF1 to TRAF6) is a bona fide PIP-binding domain. Molecular and structural analyses revealed that the TRAF domain of TRAF4 exists as a trimer that binds up to three lipids using basic residues exposed at its surface. Cellular studies indicated that TRAF4 acts as a negative regulator of TJ and increases cell migration. These functions are dependent from its ability to interact with PIPs. Our results suggest that TRAF4 overexpression might contribute to breast cancer progression by destabilizing TJs and favoring cell migration.     

Blind killing of both male and female Drosophila embryos by a natural variant of the endosymbiotic bacterium Spiroplasma poulsonii

Spiroplasma poulsonii is a vertically transmitted endosymbiont of Drosophila melanogaster that causes male‐killing, that is the death of infected male embryos during embryogenesis. Here, we report a natural variant of S. poulsonii that is efficiently vertically transmitted yet does not selectively kill males, but kills rather a subset of all embryos regardless of their sex, a phenotype we call ‘blind‐killing’. We show that the natural plasmid of S. poulsonii has an altered structure: Spaid, the gene coding for the male‐killing toxin, is deleted in the blind‐killing strain, confirming its function as a male‐killing factor. Then we further investigate several hypotheses that could explain the sex‐independent toxicity of this new strain on host embryos. As the second non‐male‐killing variant isolated from a male‐killing original population, this new strain raises questions on how male‐killing is maintained or lost in fly populations. As a natural knock‐out of Spaid, which is unachievable yet by genetic engineering approaches, this variant also represents a valuable tool for further investigations on the male‐killing mechanism.     

Circular dichroism studies of freeze-drying-induced conformational changes in human hemoglobin

Freeze-drying of hemoglobin leads to the formation of a significant amount of methemoglobin. It is possible to decrease this transformation in the presence of protective compounds. The mechanism of action of these protectors is presently unknown. Spectroscopic absorption and CD spectra between 190 and 700 nm are presented for samples of hemoglobin freeze-dried with or without protection and for control solutions of oxyhemoglobin and methemoglobin. The interpretation of the dichroic spectra allows us to observe the secondary, tertiary, and quaternary structure changes that hemoglobin undergoes with freeze-drying. The results indicate that the absence of a protector weakly influences the conformation in the vicinity of the heme and increases the helicity of protein chains from 75 to 81%. Furthermore, experimental data, in agreement with electron-spin resonance measurements, suggest that the protective effect is not the result of a direct bond between the iron and the compound added.     

The crop milk: a potential new route for carotenoid-mediated parental effects

Allocation of carotenoid pigments, either through nutritional provisioning or from endogenous reserves, makes up a form of non-genetic parental investment to progeny that may contribute to fitness. To date, carotenoids derived from endogenous reserves have been acknowledged as important vectors in translating only avian female phenotype and environmental conditions experienced prior to laying. Here, we show that in columbidae, crop milk delivered by both parents may provide chicks with a large amount of endogenous carotenoids at the postzygotic stage. Major carotenoids were xanthophylls and beta-carotene, but their concentrations showed large variation among individuals. Interestingly, a large amount of this variation was explained by brood identity, suggesting either environmental influences and/or phenotypic influences on a parent's ability to transfer these biomolecules. Our study therefore illuminates a potential new route for endogenous carotenoid-mediated parental effects.