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G protein-coupled receptors (GPCRs) mediate cellular responses to a variety of stimuli, but how specific responses are regulated has been elusive, as the types of GPCRs vastly outnumber the classes of G protein heterotrimers available to initiate downstream signaling. In our analysis of signaling proteins containing DEP domains (∼90 residue sequence motifs first recognized in fly Dishevelled, worm...
The cues governing cardiac cell-fate decisions, cardiac differentiation, and three-dimensional morphogenesis are rapidly being elucidated. Several themes are emerging that are relevant for childhood and adult heart disease and the growing field of stem cell biology. This review will consider our current understanding of cardiac cell-fate determination and cardiogenesis—largely derived from developmental...
Recent work provides new insights into the regulation of fertility in animals, plants, and unicellular eukaryotes. These findings suggest that fertility is controlled by the dynamic and complex interplay of numerous factors including the regulation of RNA stability, protein translation, chromatin structure, and chromosomal organization.
Cytosine methylation plays a crucial role in the regulation of gene expression and the control of genome stability in higher eukaryotes. Despite its importance for normal development, the degree and genome-wide distribution of DNA methylation has remained largely unknown. In this issue of Cell, Zhang et al. (2006) fill this gap by presenting a high-resolution map of DNA methylation in the genome of...
Meiosis includes a reductional division in which homologous chromosomes, rather than sister chromatids, are segregated to opposite poles of the spindle. In this issue of Cell, Petronczki et al. (2006) report that casein kinase 1 contributes to this process by promoting the attachment of both kinetochores of a homolog to only one pole of the meiotic spindle in budding yeast.
Caspase-1 promotes both the maturation of proinflammatory cytokines and apoptosis in cells infected by certain pathogens. Work by Gurcel et al. (2006) now reveals a surprising new function for caspase-1: the stimulation of membrane biogenesis to repair damage caused by bacterial pore-forming toxins. Thus, caspase-1 may promote host cell survival as a means of resistance to pathogenic bacteria.
In meiosis, a single round of DNA replication is followed by two consecutive rounds of chromosome segregation, called meiosis I and II. Disjunction of maternal from paternal centromeres during meiosis I depends on the attachment of sister kinetochores to microtubules emanating from the same pole. In budding yeast, monopolar attachment requires recruitment to kinetochores of the monopolin complex....
Despite an ever-expanding database of sequenced mammalian genomes to be mined for clues, the emergence of the unique human brain remains an evolutionary enigma. In their new study, Pollard et al. (2006) trawl the human genome and those of other mammals in search of short conserved DNA elements that show extremely rapid evolution only in humans. As they report in a recent issue of Nature, their scan...
Many pathogenic organisms produce pore-forming toxins as virulence factors. Target cells however mount a response to such membrane damage. Here we show that toxin-induced membrane permeabilization leads to a decrease in cytoplasmic potassium, which promotes the formation of a multiprotein oligomeric innate immune complex, called the inflammasome, and the activation of caspase-1. Further, we find that...
We present rna22, a method for identifying microRNA binding sites and their corresponding heteroduplexes. Rna22 does not rely upon cross-species conservation, is resilient to noise, and, unlike previous methods, it first finds putative microRNA binding sites in the sequence of interest, then identifies the targeting microRNA. Computationally, we show that rna22 identifies most of the currently known...
Our understanding of the mechanism of protein synthesis has undergone rapid progress in recent years as a result of low-resolution X-ray and cryo-EM structures of ribosome functional complexes and high-resolution structures of ribosomal subunits and vacant ribosomes. Here, we present the crystal structure of the Thermus thermophilus 70S ribosome containing a model mRNA and two tRNAs at 3.7 Å resolution...
Abscisic acid (ABA) is a phytohormone critical for plant growth, development, and adaptation to various stress conditions. Plants have to adjust ABA levels constantly to respond to changing physiological and environmental conditions. To date, the mechanisms for fine-tuning ABA levels remain elusive. Here we report that AtBG1, a β-glucosidase, hydrolyzes glucose-conjugated, biologically inactive ABA...
The KtrAB ion transporter is a complex of the KtrB membrane protein and KtrA, an RCK domain. RCK domains regulate eukaryotic and prokaryotic membrane proteins involved in K + transport. Conflicting functional models have proposed two different oligomeric arrangements for RCK domains, tetramer versus octamer. Our results for the KtrAB RCK domain clearly show an octamer in solution and in the...
IL-17-producing T lymphocytes have been recently shown to comprise a distinct lineage of proinflammatory T helper cells, termed Th17 cells, that are major contributors to autoimmune disease. We show here that the orphan nuclear receptor RORγt is the key transcription factor that orchestrates the differentiation of this effector cell lineage. RORγt induces transcription of the genes encoding IL-17...
Bacteria sense their environment using receptors of the histidine sensor kinase family, but how kinase activity is regulated by ligand binding is not well understood. Autoinducer-2 (AI-2), a secreted signaling molecule originally identified in studies of the marine bacterium Vibrio harveyi, regulates quorum-sensing responses and allows communication between different bacterial species. AI-2 signal...
This year the Lasker Foundation pays tribute to telomerase, a medically important enzyme required for chromosome stability and long-term cell proliferation.
The hormone abscisic acid regulates development and survival of plants in response to environmental stresses. Lee et al. (2006) now demonstrate that in response to stress, abscisic acid can be made available via polymerization of a β-glucosidase enzyme. This enzyme is reported to hydrolyze glucose-conjugated abscisic acid, thus increasing active abscisic acid concentrations.
Cytosine methylation is important for transposon silencing and epigenetic regulation of endogenous genes, although the extent to which this DNA modification functions to regulate the genome is still unknown. Here we report the first comprehensive DNA methylation map of an entire genome, at 35 base pair resolution, using the flowering plant Arabidopsis thaliana as a model. We find that pericentromeric...
MthK is a prokaryotic Ca 2+ -gated K + channel that, like other ligand-gated channels, converts the chemical energy of ligand binding to the mechanical force of channel opening. The channel's eight ligand-binding domains, the RCK domains, form an octameric gating ring in which Ca 2+ binding induces conformational changes that open the channel. Here we present the crystal structures...
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