Oxidative Stress-Induced STIM2 Cysteine Modifications Suppress Store-Operated Calcium Entry

Store-operated calcium entry (SOCE) through STIM-gated ORAI channels governs vital cellular functions. In this context, SOCE controls cellular redox signaling and is itself regulated by redox modifications. However, the molecular mechanisms underlying this calcium-redox interplay and the functional outcomes are not fully understood. Here, we examine the role of STIM2 in SOCE redox regulation. Redox proteomics identify cysteine 313 as the main redox sensor of STIM2 in vitro and in vivo. Oxidative stress suppresses SOCE and calcium currents in cells overexpressing STIM2 and ORAI1, an effect that is abolished by mutation of cysteine 313. FLIM and FRET microscopy, together with MD simulations, indicate that oxidative modifications of cysteine 313 alter STIM2 activation dynamics and thereby hinder STIM2-mediated gating of ORAI1. In summary, this study establishes STIM2-controlled redox regulation of SOCE as a mechanism that affects several calcium-regulated physiological processes, as well as stress-induced pathologies

Actin-Related Protein Arp6 Influences H2A.Z-Dependent and -Independent Gene Expression and Links Ribosomal Protein Genes to Nuclear Pores

Actin-related proteins are ubiquitous components of chromatin remodelers and are conserved from yeast to man. We have examined the role of the budding yeast actin-related protein Arp6 in gene expression, both as a component of the SWR1 complex (SWR-C) and in its absence. We mapped Arp6 binding sites along four yeast chromosomes using chromatin immunoprecipitation from wild-type and swr1 deleted (swr1Δ) cells. We find that a majority of Arp6 binding sites coincide with binding sites of Swr1, the catalytic subunit of SWR-C, and with the histone H2A variant Htz1 (H2A.Z) deposited by SWR-C. However, Arp6 binding detected at centromeres, the promoters of ribosomal protein (RP) genes, and some telomeres is independent of Swr1 and Htz1 deposition. Given that RP genes and telomeres both show association with the nuclear periphery, we monitored the ability of Arp6 to mediate the localization of chromatin to nuclear pores. Arp6 binding is sufficient to shift a randomly positioned locus to nuclear periphery, even in a swr1Δ strain. Arp6 is also necessary for the pore association of its targeted RP promoters possibly through cell cycle-dependent factors. Loss of Arp6, but not Htz1, leads to an up-regulation of these RP genes. In contrast, the pore-association of GAL1 correlates with Htz1 deposition, and loss of Arp6 reduces both GAL1 activation and peripheral localization. We conclude that Arp6 functions both together with the nucleosome remodeler Swr1 and also without it, to mediate Htz1-dependent and Htz1-independent binding of chromatin domains to nuclear pores. This association is shown to have modulating effects on gene expression

The Solute Carrier Families Have a Remarkably Long Evolutionary History with the Majority of the Human Families Present before Divergence of Bilaterian Species

The Solute Carriers (SLCs) are membrane proteins that regulate transport of many types of substances over the cell membrane. The SLCs are found in at least 46 gene families in the human genome. Here, we performed the first evolutionary analysis of the entire SLC family based on whole genome sequences. We systematically mined and analyzed the genomes of 17 species to identify SLC genes. In all, we identified 4,813 SLC sequences in these genomes, and we delineated the evolutionary history of each of the subgroups. Moreover, we also identified ten new human sequences not previously classified as SLCs, which most likely belong to the SLC family. We found that 43 of the 46 SLC families found in Homo sapiens were also found in Caenorhabditis elegans, whereas 42 of them were also found in insects. Mammals have a higher number of SLC genes in most families, perhaps reflecting important roles for these in central nervous system functions. This study provides a systematic analysis of the evolutionary history of the SLC families in Eukaryotes showing that the SLC superfamily is ancient with multiple branches that were present before early divergence of Bilateria. The results provide foundation for overall classification of SLC genes and are valuable for annotation and prediction of substrates for the many SLCs that have not been tested in experimental transport assays

Affective economies, pandas, and the atmospheric politics of lively capital

This paper is concerned with the affective economies of lively capital. Its central argument is that nonhuman life itself has become a locus of accumulation, marked by an atmospheric politics of capital: the intensification of relations between life and productivity by incorporating entire lifeworlds into regimes of generating value. Focusing on the Giant panda – a spectacular icon raising millions of dollars globally – the paper first examines junctures at which their charismatic affects emerge and are manipulated to produce value. Turning to panda lifeworlds in zoos, it then shows how such value production is contingent upon affective labours nonhumans perform in captivity. Nonhuman labour, as a component of atmospheric politics, enables understanding how lively capital is produced and reproduced, a theme interrogated through a critical analysis of the commercial global circulation of pandas. The paper develops the concept of atmospheric politics – an intervention in an animal’s milieu and its affective intensities – as a means for analyzing the dynamics of lively capital. Atmospheric politics retrieves a critical political economy obscured by the concept of nonhuman charisma, and restages biopower as an apparatus and political technology of capital.Parts of the research conducted for this paper was enabled by a British Academy Postdoctoral Fellowship (Award No. pf140038)

Structural constraints for the Crh protein from solid-state NMR experiments

We demonstrate that short, medium and long-range constraints can be extracted from proton mediated, rare-spin detected correlation solid-state NMR experiments for the microcrystalline 10.4 × 2 kDa dimeric model protein Crh. Magnetization build-up curves from cross signals in NHHC and CHHC spectra deliver detailed information on side chain conformers and secondary structure for interactions between spin pairs. A large number of medium and long-range correlations can be observed in the spectra, and an analysis of the resolved signals reveals that the constraints cover the entire sequence, also including inter-monomer contacts between the two molecules forming the domain-swapped Crh dimer. Dynamic behavior is shown to have an impact on cross signals intensities, as indicated for mobile residues or regions by contacts predicted from the crystal structure, but absent in the spectra. Our work validates strategies involving proton distance measurements for large and complex proteins as the Crh dimer, and confirms the magnetization transfer properties previously described for small molecules in solid protein samples

Body mass index, adiposity rebound and early feeding in a longitudinal cohort (Raine study)

Objective: This study examined the influence of type and duration of infant feeding on adiposity rebound and the tracking of body mass index (BMI) from birth to 14 years. Methods: A sample of 1330 individuals over eight follows-ups was drawn from the Western Australian Pregnancy Cohort (Raine) Study. Trajectories of BMI from birth to adolescence using linear mixed model (LMM) analysis investigated the influence of age breastfeeding stopped and age other milk introduced (binomial 4-month cut-point). A sub-sample of LMM predicted BMI was used to determine BMI and age at nadir for early infant feeding groups. Results: Chi square analysis between early feeding and weight status (normal weight, overweight and obese) groups found a significant difference between age breastfeeding stopped (p Conclusions: Early infant feeding was important in the timing and BMI at adiposity rebound. The relationship between infant feeding and BMI remained up to age 14 years. Although confounding factors cannot be excluded, these findings support the importance of exclusive breastfeeding for longer than four months as a protective behaviour against the development of adolescent obesity