A. Athane

CaMKII-dependent phosphorylation of GluK5 mediates plasticity of kainate receptors

Calmodulin‐dependent kinase II (CaMKII) is key for long‐term potentiation of synaptic AMPA receptors. Whether CaMKII is involved in activity‐dependent plasticity of other ionotropic glutamate receptors is unknown. We show that repeated pairing of pre‐ and postsynaptic stimulation at hippocampal mossy fibre synapses induces long‐term depression of kainate receptor (KAR)‐mediated responses, which depends on Ca2+ influx, activation of CaMKII, and on the GluK5 subunit of KARs. CaMKII phosphorylation of three residues in the C‐terminal domain of GluK5 subunit markedly increases lateral mobility of KARs, possibly by decreasing the binding of GluK5 to PSD‐95. CaMKII activation also promotes surface expression of KARs at extrasynaptic sites, but concomitantly decreases its synaptic content. Using a molecular replacement strategy, we demonstrate that the direct phosphorylation of GluK5 by CaMKII is necessary for KAR‐LTD. We propose that CaMKII‐dependent phosphorylation of GluK5 is responsible for synaptic depression by untrapping of KARs from the PSD and increased diffusion away from synaptic sites.

Effect of In Utero Wi-Fi Exposure on the Pre- and Postnatal Development of Rats

BACKGROUND The increase in exposure to the Wireless Fidelity (Wi-Fi) wireless communication signal has raised public health concerns especially for young people. Animal studies looking at the effects of early life and prenatal exposure to this source of electromagnetic fields, in the radiofrequency (RF) range, on development and behavior have been considered as high priority research needs by the World Health Organization. METHODS For the first time, our study assessed the effects of in utero exposure to a 2450 MHz Wi-Fi signal (2 hr/day, 6 days/week for 18 days) on pregnant rats and their pups. Three levels in terms of whole-body specific absorption rate were used: 0.08, 0.4, and 4 W/kg. The prenatal study on fetuses delivered by caesarean (P20) concerned five females/group. The dams and their offspring were observed for 28 days after delivery (15 females/group). RESULTS For all test conditions, no abnormalities were noted in the pregnant rats and no significant signs of toxicity were observed in the pre- and postnatal development of the pups, even at the highest level of 4 W/kg. CONCLUSIONS In the present study, no teratogenic effect of repeated exposures to the Wi-Fi wireless communication signal was demonstrated even at the highest level of 4 W/kg. The results from this screening study aimed at investigating Wi-Fi effects, strengthen the previous conclusions that teratology and development studies have not detected any noxious effects of exposures to mobile telephony-related RF fields at exposure levels below standard limits.

Bcl-xL stimulates Bax relocation to mitochondria and primes cells to ABT-737

Bax cytosol-to-mitochondria translocation is a central event of the intrinsic pathway of apoptosis. Bcl-xL is an important regulator of this event and was recently shown to promote the retrotranslocation of mitochondrial Bax to the cytosol. The present study identifies a new aspect of the regulation of Bax localization by Bcl-xL: in addition to its role in Bax inhibition and retrotranslocation, we found that, like with Bcl-2, an increase of Bcl-xL expression levels led to an increase of Bax mitochondrial content. This finding was substantiated both in pro-lymphocytic FL5.12 cells and a yeast reporting system. Bcl-xL-dependent increase of mitochondrial Bax is counterbalanced by retrotranslocation, as we observed that Bcl-xLΔC, which is unable to promote Bax retrotranslocation, was more efficient than the full-length protein in stimulating Bax relocation to mitochondria. Interestingly, cells overexpressing Bcl-xL were more sensitive to apoptosis upon treatment with the BH3-mimetic ABT-737, suggesting that despite its role in Bax inhibition, Bcl-xL also primes mitochondria to permeabilization and cytochrome c release.

Characterization of an acquired dps‐containing gene island in the lactic acid bacterium Oenococcus oeni

Aims:  To identify novel actors responsible for the marked adaptation of the Oenococcus oeni species to its environment.

Insights into the relationship between the proteasome and autophagy in human and yeast cells.

In eukaryotes, the ubiquitin-proteasome system (UPS) and autophagy are two major intracellular protein degradation pathways. Several lines of evidence support the emerging concept of a coordinated and complementary relationship between these two processes, and a particularly interesting finding is that the inhibition of the proteasome induces autophagy. Yet, there is limited knowledge of the regulation of the UPS by autophagy. In this study, we show that the disruption of ATG5 and ATG32 genes in yeast cells under both nutrient-deficient conditions as well as stress that causes mitochondrial dysfunction leads to an activation of proteasome. The same scenario occurs after pharmacological inhibition of basal autophagy in cultured human cells. Our findings underline the view that the two processes are interconnected and tend to compensate, to some extent, for each others functions.