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Many biological motor molecules move within cells using stepsizes predictable from their structures. Myosin VI, however, has much larger and more broadly distributed stepsizes than those predicted from its short lever arms. We explain the discrepancy by monitoring Qdots and gold nanoparticles attached to the myosin-VI motor domains using high-sensitivity nanoimaging. The large stepsizes were attributed...
We present evidence for a coupled two-step action of Hedgehog signaling in patterning axon targeting of Drosophila olfactory receptor neurons (ORNs). In the first step, differential Hedgehog pathway activity in peripheral sensory organ precursors creates ORN populations with different levels of the Patched receptor. Different Patched levels in ORNs then determine axonal responsiveness to target-derived...
DNA transactions driven by long-range protein-mediated inter- and intrachromosomal interactions have been reported to influence gene expression. Here, we report that site-specific replication termination in Schizosaccharomyces pombe is modulated by protein-mediated interactions between pairs of Ter sites located either on the same or on different chromosomes. The dimeric Reb1 protein catalyzes termination...
Identifying proteins that recognize histone methylation is critical for understanding chromatin function. Vermeulen et al. (2010) now describe a cutting-edge strategy to identify and characterize several nuclear proteins and complexes that recognize five major histone trimethyl marks.
Alzheimer's Disease (AD) is complicated by pro-oxidant intraneuronal Fe 2+ elevation as well as extracellular Zn 2+ accumulation within amyloid plaque. We found that the AD β-amyloid protein precursor (APP) possesses ferroxidase activity mediated by a conserved H-ferritin-like active site, which is inhibited specifically by Zn 2+ . Like ceruloplasmin, APP catalytically oxidizes...
Many viruses utilize host ESCRT proteins for budding; however, influenza virus budding is thought to be ESCRT-independent. In this study we have found a role for the influenza virus M2 proton-selective ion channel protein in mediating virus budding. We observed that a highly conserved amphipathic helix located within the M2 cytoplasmic tail mediates a cholesterol-dependent alteration in membrane curvature...
Although genome-wide hypomethylation is a hallmark of many cancers, roles for active DNA demethylation during tumorigenesis are unknown. Here, loss of the APC tumor suppressor gene causes upregulation of a DNA demethylase system and the concomitant hypomethylation of key intestinal cell fating genes. Notably, this hypomethylation maintained zebrafish intestinal cells in an undifferentiated state that...
Natural killer (NK) cells play a key role in the immune response to certain infections and malignancies by direct cytolysis of infected or transformed cells and by secretion of potent immune mediators. NK cells express an array of activating receptors that recognize self-molecules. If not restrained by inhibitory receptors recognizing major histocompatibility complex (MHC) class I proteins on the...
At noon on September 18 th , 2010, the mayor of Munich will kick off Oktoberfest with the traditional “O'zapft is” as he taps the first keg of the festival. Over the course of the next 2 weeks, more than six million people will celebrate the 200 th anniversary of Oktoberfest by savoring roasted chicken, juicy weisswurst, and giant pretzels. But, most importantly, there will be beer—enough...
Many enveloped viruses depend on the membrane remodeling machinery of their host cells to complete their life cycle. In this issue, Rossman et al. (2010) now demonstrate that influenza virus possesses its own device for releasing nascent virus particles from the plasma membrane, the M2 proton-selective ion channel, which can substitute for the host cell's ESCRT pathway.
Trimethyl-lysine (me3) modifications on histones are the most stable epigenetic marks and they control chromatin-mediated regulation of gene expression. Here, we determine proteins that bind these marks by high-accuracy, quantitative mass spectrometry. These chromatin “readers” are assigned to complexes by interaction proteomics of full-length BAC-GFP-tagged proteins. ChIP-Seq profiling identifies...
Circadian clocks in peripheral organs are tightly coupled to cellular metabolism and are readily entrained by feeding-fasting cycles. However, the molecular mechanisms involved are largely unknown. Here we show that in liver the activity of PARP-1, an NAD + -dependent ADP-ribosyltransferase, oscillates in a daily manner and is regulated by feeding. We provide biochemical evidence that PARP-1...
In response to many apoptotic stimuli, oligomerization of Bax is essential for mitochondrial outer membrane permeabilization and the ensuing release of cytochrome c. These events are accompanied by mitochondrial fission that appears to require Drp1, a large GTPase of the dynamin superfamily. Loss of Drp1 leads to decreased cytochrome c release by a mechanism that is poorly understood. Here we show...
Cells possess internal ∼24 hr or circadian clocks that synchronize physiological processes with daily cycles of light and nutrient availability. In this issue, Asher et al. (2010) find that PARP-1 (poly(ADP-ribose) polymerase 1) modifies components of the clock machinery in response to feeding, providing a mechanism for how metabolic rhythms coordinate with circadian rhythms.
Foxp3 + regulatory T (Treg) cells maintain immune homeostasis by limiting different types of inflammatory responses. Here, we report that miR-146a, one of the miRNAs prevalently expressed in Treg cells, is critical for their suppressor function. The deficiency of miR-146a in Treg cells resulted in a breakdown of immunological tolerance manifested in fatal IFNγ-dependent immune-mediated lesions...
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