Wednesday, November 10, 2010

Hot off the presses! Nov 09 curr biol

The Nov 09 issue of the curr biol is now up on Pubget (About curr biol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

  • Britain cuts back deeply on spending
    - curr biol 20(21):R905-R906 (2010)
    The UK government has revealed its spending plans for the next four years with cuts affecting science, higher education and environmental projects. Michael Gross reports.
  • Fresh advice on climate change
    - curr biol 20(21):R907-R908 (2010)
    Ahead of the key Cancun meeting on global controls on greenhouse gas emissions, Britain's Royal Society has issued its assessment of the scientific evidence underlying the issues. Nigel Williams reports.
  • New language found
    - curr biol 20(21):R909 (2010)
    As human languages are increasingly dying out, the discovery of a new one is striking. Nigel Williams reports.
  • Deep ocean species discovered
    - curr biol 20(21):R909-R910 (2010)
    One of the world's deepest ocean trenches has revealed surprises. Nigel Williams reports.
  • Sara J. Shettleworth
    - curr biol 20(21):R910-R911 (2010)
  • Pandering to the pandas
    - curr biol 20(21):R912 (2010)
  • Animal personality
    - curr biol 20(21):R912-R914 (2010)
  • Carnivores
    - curr biol 20(21):R915-R919 (2010)
    The mammalian order Carnivora includes species we most love and fear — our household pets, dogs and cats, and large predators such as bears, lions, and wolves. Our fondness for domesticated carnivores is reflected in sheer numbers: the estimated number of household cats and dogs exceeds 100 million each, a global population size that easily outdistances that of any wild carnivore. By contrast, large predators are among the most endangered of mammals and conservation efforts to expand their numbers always face stiff opposition. Our relationship with large carnivores is complex and fraught with conflict; on the one hand we admire their strength and beauty, and see parallels between ourselves and group hunters, such as gray wolves and lions. On the other hand, we feel compelled to tightly control their numbers, and have completely extirpated them from large parts of the world.
  • A spliceosomal intron of mitochondrial DNA origin
    - curr biol 20(21):R919-R920 (2010)
    The origin of spliceosomal introns is one of the most enduring mysteries in molecular biology. In nuclear genomes such as our own, the protein-coding regions of genes (exons) can be separated from one another by hundreds of thousands of base pairs (bp) of intronic (non-coding) DNA, and while they are often considered 'junk', introns are increasingly ascribed important regulatory functions [1]. Here we present evidence that an intron in a GTPase superfamily gene in the unicellular alga Bigelowiella natans is derived from — and was created by — the insertion of a fragment of mitochondrial DNA. Organelle-to-nucleus DNA transfer is an increasingly well-understood phenomenon, one that has the potential to greatly influence genome structure [2] and [3]. Our data suggest that such transfers could represent a hitherto underappreciated source of new spliceosomal introns.
  • Brain development after birth differs between Neanderthals and modern humans
    - curr biol 20(21):R921-R922 (2010)
    Neanderthals had brain sizes comparable to modern humans, but their brain cases were elongated and not globular as in Homo sapiens[1] and [2]. It has, therefore, been suggested that modern humans and Neanderthals reached large brain sizes along different evolutionary pathways [2]. Here, we assess when during development these adult differences emerge. This is critical for understanding whether differences in the pattern of brain development might underlie potential cognitive differences between these two closely related groups. Previous comparisons of Neanderthal and modern human cranial development have shown that many morphological characteristics separating these two groups are already established at the time of birth [3], [4] and [5], and that the subsequent developmental patterns of the face are similar, though not identical [6]. Here, we show that a globularization phase seen in the neurocranial development of modern humans after birth is absent from Neanderthals.
  • Nuclear Membrane: Nuclear Envelope PORosity in Fission Yeast Meiosis
    - curr biol 20(21):R923-R925 (2010)
    The fission yeast Schizosaccharomyces pombe undergoes closed mitosis but 'virtual nuclear envelope breakdown' at anaphase of meiosis II, in which the nuclear envelope is structurally closed but functionally open.
  • Reproductive Strategies: How Big Is Your Love?
    - curr biol 20(21):R925-R928 (2010)
    In swordtails, gene copy number variation is associated with alternative male mating strategies, size and puberty. Though it is unclear how the different aspects are linked mechanistically, the nature of the gene, a melanocortin receptor, suggests avenues for future inquiry.
  • Ciliary Trafficking: CEP290 Guards a Gated Community
    - curr biol 20(21):R928-R931 (2010)
    A recent study reveals that the large coiled-coil protein CEP290 is an integral component of the transition zone between the cell body and the cilium and functions as a gatekeeper to regulate trafficking of ciliary proteins.
  • Communal Breeding: Clever Defense Against Cheats
    - curr biol 20(21):R931-R933 (2010)
    High levels of conspecific brood parasitism are found in a communally breeding bird, with implications for the evolutionary links between brood parasitism and communal breeding. It also uncovers a novel egg recognition mechanism hosts use to foil brood parasites.
  • Brain Development: Critical Periods for Cross-Sensory Plasticity
    - curr biol 20(21):R934-R936 (2010)
    Recent work has shown that visual deprivation of humans during a critical period leads to motion area MT+ responding to auditory motion. This cross-sensory plasticity, an important form of brain reorganization, may be mediated by top-down brain circuits from pre-frontal cortex.
  • Mechanosensitive Channels: In Touch with Piezo
    - curr biol 20(21):R936-R938 (2010)
    Mechanosensory transduction underlies touch, hearing and proprioception and requires mechanosensitive channels that are directly gated by forces; however, the molecular identities of these channels remain largely elusive. A new study has identified Piezo1 and Piezo2 as a novel class of mechanosensitive channels.
  • Marine Connectivity: Timing Is Everything
    - curr biol 20(21):R938-R940 (2010)
    Marine populations are connected through planktonic larvae that are dispersed at the whim of currents. But, living together does not mean dispersing together: connectivity depends not just on where you breed, but also on when you breed.
  • Apoptosis: Opening PANdora's BoX
    - curr biol 20(21):R940-R942 (2010)
    Extracellular nucleotides have been reported to act as a 'find-me' signal in the context of phagocyte recruitment by apoptotically dying cells. A new study now examines the mechanisms of nucleotide release during apoptosis and describes the hemichannel-forming protein pannexin 1 as a crucial player in this scenario.
  • Multisubunit Tethering Complexes and Their Role in Membrane Fusion
    - curr biol 20(21):R943-R952 (2010)
    Protein trafficking within eukaryotic cells depends on vesicular carriers that fuse with organelles to deliver their lipid and protein content. Cells have developed an elaborate system to capture vesicles at organelles that involves the action of Rab GTPases and tethers. Vesicle fusion then takes place with the help of SNARE proteins. In this review we focus on the role of multisubunit tethering complexes of eukaryotic cells. In particular, we discuss the tethering complexes of the secretory pathway and the endolysosomal system and highlight recent evidence for the role of these complexes in interaction with Rabs, coat recognition and cooperation with SNAREs during the fusion cascade.
  • 14-3-3 Coordinates Microtubules, Rac, and Myosin II to Control Cell Mechanics and Cytokinesis
    - curr biol 20(21):1881-1889 (2010)
    Background During cytokinesis, regulatory signals are presumed to emanate from the mitotic spindle. However, what these signals are and how they lead to the spatiotemporal changes in the cortex structure, mechanics, and regional contractility are not well understood in any system. Results To investigate pathways that link the microtubule network to the cortical changes that promote cytokinesis, we used chemical genetics in Dictyostelium to identify genetic suppressors of nocodazole, a microtubule depolymerizer. We identified 14-3-3 and found that it is enriched in the cortex, helps maintain steady-state microtubule length, contributes to normal cortical tension, modulates actin wave formation, and controls the symmetry and kinetics of cleavage furrow contractility during cytokinesis. Furthermore, 14-3-3 acts downstream of a Rac small GTPase (RacE), associates with myosin II heavy chain, and is needed to promote myosin II bipolar thick filament remodeling. Conclusions 14-3-3 connects microtubules, Rac, and myosin II to control several aspects of cortical dynamics, mechanics, and cytokinesis cell shape change. Furthermore, 14-3-3 interacts directly with myosin II heavy chain to promote bipolar thick filament remodeling and distribution. Overall, 14-3-3 appears to integrate several critical cytoskeletal elements that drive two important processes—cytokinesis cell shape change and cell mechanics.
  • Reconstitution and Protein Composition Analysis of Endocytic Actin Patches
    - curr biol 20(21):1890-1899 (2010)
    Background Clathrin-actin-mediated endocytosis in yeast involves the progressive assembly of at least 60 different proteins at cortical sites. More than half of these proteins are involved in the assembly of a branched network of actin filaments to provide the forces required for plasma membrane invagination. Results To gain insights into the regulation of endocytic actin patch dynamics, we developed an in vitro actin assembly assay using microbeads functionalized with the nucleation promoting factor (NPF) Las17 (yeast WASP). When incubated in a yeast extract, these beads assembled actin networks, and a significant fraction became motile. Multidimensional protein identification technology (MudPIT) showed that the recruitment of actin-binding proteins to these Las17-derived actin networks is selective. None of the proteins known to exclusively regulate the in vivo formation of actin cables or the actin contractile ring were identified. Our analysis also identified components of three other cortical structures, eisosomes, phosphoinositide kinase (PIK) patches, and the TORC2 complex, establishing intriguing biochemical connections between four different yeast cortical complexes. Finally, we identified Aim3 as a regulator of actin dynamics at endocytic sites. Conclusions WASP is sufficient to trigger assembly of actin networks composed selectively of actin patch proteins. These experiments establish that the protein composition of different F-actin structures is determined by the protein factor that initiates the network. The identification of binding partners revealed new biochemical connections between WASP-derived networks and other cortical complexes and identified Aim3 as a novel regulator of the endocytic actin patch.
  • Sensitive Period for a Multimodal Response in Human Visual Motion Area MT/MST
    - curr biol 20(21):1900-1906 (2010)
    The middle temporal complex (MT/MST) is a brain region specialized for the perception of motion in the visual modality [[1], [2], [3] and [4]]. However, this specialization is modified by visual experience: after long-standing blindness, MT/MST responds to sound [5]. Recent evidence also suggests that the auditory response of MT/MST is selective for motion [[6] and [7]]. The developmental time course of this plasticity is not known. To test for a sensitive period in MT/MST development, we used fMRI to compare MT/MST function in congenitally blind, late-blind, and sighted adults. MT/MST responded to sound in congenitally blind adults, but not in late-blind or sighted adults, and not in an individual who lost his vision between ages of 2 and 3 years. All blind adults had reduced functional connectivity between MT/MST and other visual regions. Functional connectivity was increased between MT/MST and lateral prefrontal areas in congenitally blind relative to sighted and la! te-blind adults. These data suggest that early blindness affects the function of feedback projections from prefrontal cortex to MT/MST. We conclude that there is a sensitive period for visual specialization in MT/MST. During typical development, early visual experience either maintains or creates a vision-dominated response. Once established, this response profile is not altered by long-standing blindness.
  • Physcomitrella patens Auxin-Resistant Mutants Affect Conserved Elements of an Auxin-Signaling Pathway
    - curr biol 20(21):1907-1912 (2010)
    Auxin regulates most aspects of flowering-plant growth and development, including key developmental innovations that evolved within the vascular plant lineage after diverging from a bryophyte-like ancestor nearly 500 million years ago [[1], [2] and [3]]. Recent studies in Arabidopsis indicate that auxin acts by directly binding the TIR1 subunit of the SCFTIR1 ubiquitin ligase; this binding results in degradation of the Aux/IAA transcriptional repressors and de-repression of auxin-responsive genes [[4], [5], [6], [7], [8] and [9]]. Little is known, however, about the mechanism of auxin action in other plants. To characterize auxin signaling in a nonflowering plant, we utilized the genetically tractable moss Physcomitrella patens. We used a candidate-gene approach to show that previously identified auxin-resistant mutants of P. patens harbor mutations in Aux/IAA genes. Furthermore, we show that the moss Aux/IAA proteins interact with Arabidopsis TIR1 moss homologs called! PpAFB and that a reduction in PpAFB levels results in a phenotype similar to that of the auxin-resistant mutants. Our results indicate that the molecular mechanism of auxin perception is conserved in land plants despite vast differences in the role auxin plays in different plant lineages.
  • Nuclear Compartmentalization Is Abolished during Fission Yeast Meiosis
    - curr biol 20(21):1913-1918 (2010)
    In eukaryotic cells, the nuclear envelope partitions the nucleus from the cytoplasm. The fission yeast Schizosaccharomyces pombe undergoes closed mitosis in which the nuclear envelope persists rather than being broken down, as in higher eukaryotic cells [1]. It is therefore assumed that nucleocytoplasmic transport continues during the cell cycle [2]. Here we show that nuclear transport is, in fact, abolished specifically during anaphase of the second meiotic nuclear division. During that time, both nucleoplasmic and cytoplasmic proteins disperse throughout the cell, reminiscent of the open mitosis of higher eukaryotes, but the architecture of the S. pombe nuclear envelope itself persists. This functional alteration of the nucleocytoplasmic barrier is likely induced by spore wall formation, because ectopic induction of sporulation signaling leads to premature dispersion of nucleoplasmic proteins. A photobleaching assay demonstrated that nuclear envelope permeability inc! reases abruptly at the onset of anaphase of the second meiotic division. The permeability was not altered when sporulation was inhibited by blocking the trafficking of forespore-membrane vesicles from the endoplasmic reticulum to the Golgi. The evidence indicates that yeast gametogenesis produces vesicle transport-mediated forespore membranes by inducing nuclear envelope permeabilization.
  • Virtual Breakdown of the Nuclear Envelope in Fission Yeast Meiosis
    - curr biol 20(21):1919-1925 (2010)
    Asymmetric localization of Ran regulators (RanGAP1 and RanGEF/RCC1) produces a gradient of RanGTP across the nuclear envelope [1]. In higher eukaryotes, the nuclear envelope breaks down as the cell enters mitosis (designated "open" mitosis). This nuclear envelope breakdown (NEBD) leads to collapse of the RanGTP gradient and the diffusion of nuclear and cytoplasmic macromolecules in the cell, resulting in irreversible progression of the cell cycle [[2], [3], [4], [5], [6] and [7]]. On the other hand, in many fungi, chromosome segregation takes place without NEBD (designated "closed" mitosis). Here we report that in the fission yeast Schizosaccharomyces pombe, despite the nuclear envelope and the nuclear pore complex remaining intact throughout both the meiotic and mitotic cell cycles, nuclear proteins diffuse into the cytoplasm transiently for a few minutes at the onset of anaphase of meiosis II. We also found that nuclear protein diffusion into the cytoplasm oc! curred coincidently with nuclear localization of Rna1, an S. pombe RanGAP1 homolog that is usually localized in the cytoplasm. These results suggest that nuclear localization of RanGAP1 and depression of RanGTP activity in the nucleus may be mechanistically tied to meiosis-specific diffusion of nuclear proteins into the cytoplasm. This nucleocytoplasmic shuffling of RanGAP1 and nuclear proteins represents virtual breakdown of the nuclear envelope.
  • Reproductive Timing Alters Population Connectivity in Marine Metapopulations
    - curr biol 20(21):1926-1931 (2010)
    Populations of most marine organisms are connected by the dispersal of larval stages, with profound implications for marine conservation [1]. Because of the extreme effort needed to empirically measure larval exchange, multispecies conservation efforts must estimate connectivity by extrapolation using taxonomy, adult distribution, life history, behavior, or phenology. Using a 6-year record of connectivity realized through trace-elemental fingerprinting of larval shells, we document the seasonal and interannual variability of larval exchange for two congeneric mussel species with overlapping but distinct distribution, life history, and reproduction timing. We reveal consistent autumn poleward movement and spring equatorward movement for both species, coincident with near-shore surface currents. However, because the major reproductive seasons differ, the dominant source-sink dynamics of these two congeneric species are nearly opposite. Consideration of present and future! reproductive timing as altered by climate change is crucial to marine connectivity and conservation, especially for the numerous coastal areas subject to seasonal current reversals.
  • Eggshell Chitin and Chitin-Interacting Proteins Prevent Polyspermy in C. elegans
    - curr biol 20(21):1932-1937 (2010)
    Development requires fertilization by a single sperm [[1] and [2]]. In Caenorhabditis elegans, fertilization occurs in a sperm-filled spermatheca, implying the barrier to polyspermy is generated in this compartment. Eggshell chitin synthesis is initiated at fertilization, and chitin is deposited before the zygote exits the spermatheca. Whereas polyspermy is very rare in wild-type, here we report an incidence of 14%–51% in zygotes made chitin deficient by loss of chitin synthase-1 (CHS-1), the CHS-1 substrate UDP-N-acetylglucosamine, the CHS-1-interacting protein EGG-3, or the sperm-provided protein SPE-11. The spe-11(hc90) mutant deposits chitin at the male end but fails to complete a continuous layer. The polyspermy barrier is also compromised by loss of the chitin-binding protein CBD-1 or the GLD-1-regulated LDL receptor-like EGG-1, together with its homolog, EGG-2. Loss of CBD-1 or EGG-1/2 disrupts oocyte cortical distribution of CHS-1, as well as MBK-2 and EGG-3.! In CBD-1 or EGG-1/2 deficiency, chitin is synthesized but the eggshell is fractured, suggesting aberrantly clustered CHS-1/MBK-2/EGG-3 may fail to support construction of a continuous eggshell. Together, our results show that eggshell chitin is required to prevent polyspermy in C. elegans, in addition to its previously reported requirement in polar body extrusion and polarization of the zygote.
  • Structural Long-Term Changes at Mushroom Body Input Synapses
    - curr biol 20(21):1938-1944 (2010)
    How does the sensory environment shape circuit organization in higher brain centers? Here we have addressed the dependence on activity of a defined circuit within the mushroom body of adult Drosophila. This is a brain region receiving olfactory information and involved in long-term associative memory formation [1]. The main mushroom body input region, named the calyx, undergoes volumetric changes correlated with alterations of experience [[2], [3], [4] and [5]]. However, the underlying modifications at the cellular level remained unclear. Within the calyx, the clawed dendritic endings of mushroom body Kenyon cells form microglomeruli, distinct synaptic complexes with the presynaptic boutons of olfactory projection neurons [[6] and [7]]. We developed tools for high-resolution imaging of pre- and postsynaptic compartments of defined calycal microglomeruli. Here we show that preventing firing of action potentials or synaptic transmission in a small, identified fraction of! projection neurons causes alterations in the size, number, and active zone density of the microglomeruli formed by these neurons. These data provide clear evidence for activity-dependent organization of a circuit within the adult brain of the fly.
  • Nucleoredoxin Sustains Wnt/β-Catenin Signaling by Retaining a Pool of Inactive Dishevelled Protein
    - curr biol 20(21):1945-1952 (2010)
    Overexpression of Dishevelled (Dvl), an essential component of the Wnt signaling pathway, is frequently associated with tumors [[1] and [2]], and thus the Dvl protein level must be tightly controlled to sustain Wnt signaling without causing tumors. Kelch-like 12 (KLHL12) targets Dvl for ubiquitination and degradation [3], suggesting its potential importance in avoiding aberrant Dvl overexpression. However, the regulatory mechanism of the KLHL12 activity remained elusive. We show here that nucleoredoxin (NRX) determines the Dvl protein level, which is revealed by analyses on NRX−/− mice showing skeletal and cardiovascular defects. Consistent with the previously reported Dvl-inhibiting function of NRX [4], Wnt/β-catenin signaling is hyperactivated in NRX−/− osteoblasts. However, the signal activity is suppressed in cardiac cells, where KLHL12 is highly expressed. Biochemical analyses reveal that Dvl is rapidly degraded by accelerated ubiquitination in NRX−/−! mouse embryonic fibroblasts, and they fail to activate Wnt/β-catenin signaling in response to Wnt ligands. Moreover, experiments utilizing purified proteins show that NRX expels KLHL12 from Dvl and inhibits ubiquitination. These findings reveal an unexpected function of NRX, retaining a pool of inactive Dvl for robust activation of Wnt/β-catenin signaling upon Wnt stimulation.
  • Localization and Activation of the Drosophila Protease Easter Require the ER-Resident Saposin-like Protein Seele
    - curr biol 20(21):1953-1958 (2010)
    Drosophila embryonic dorsal-ventral polarity is generated by a series of serine protease processing events in the egg perivitelline space. Gastrulation Defective processes Snake, which then cleaves Easter, which then processes Spätzle into the activating ligand for the Toll receptor [[1], [2] and [3]]. seele was identified in a screen for mutations that, when homozygous in ovarian germline clones, lead to the formation of progeny embryos with altered embryonic patterning; maternal loss of seele function leads to the production of moderately dorsalized embryos [4]. By combining constitutively active versions of Gastrulation Defective, Snake, Easter, and Spätzle with loss-of-function alleles of seele, we find that Seele activity is dispensable for Spätzle-mediated activation of Toll but is required for Easter, Snake, and Gastrulation Defective to exert their effects on dorsal-ventral patterning. Moreover, Seele function is required specifically for secretion of Easter! from the developing embryo into the perivitelline space and for Easter processing. Seele protein resides in the endoplasmic reticulum of blastoderm embryos, suggesting a role in the trafficking of Easter to the perivitelline space, prerequisite to its processing and function. Easter transport to the perivitelline space represents a previously unappreciated control point in the signal transduction pathway that controls Drosophila embryonic dorsal-ventral polarity.
  • Fission Yeast Mto1 Regulates Diversity of Cytoplasmic Microtubule Organizing Centers
    - curr biol 20(21):1959-1965 (2010)
    Microtubule nucleation by the γ-tubulin complex occurs primarily at centrosomes, but more diverse types of microtubule organizing centers (MTOCs) also exist, especially in differentiated cells [[1], [2], [3] and [4]]. Mechanisms generating MTOC diversity are poorly understood. Fission yeast Schizosaccharomyces pombe has multiple types of cytoplasmic MTOCs, and these vary through the cell cycle [[5] and [6]]. Cytoplasmic microtubule nucleation in fission yeast depends on a complex of proteins Mto1 and Mto2 (Mto1/2), which localizes to MTOCs and interacts with the γ-tubulin complex [[7], [8], [9], [10], [11] and [12]]. Localization of Mto1 to prospective MTOC sites has been proposed as a key step in γ-tubulin complex recruitment and MTOC formation [[9] and [13]], but how Mto1 localizes to such sites has not been investigated. Here we identify a short conserved C-terminal sequence in Mto1, termed MASC, important for targeting Mto1 to multiple distinct MTOCs. Different ! subregions of MASC target Mto1 to different MTOCs, and multimerization of MASC is important for efficient targeting. Mto1 targeting to the cell equator during division depends on direct interaction with unconventional type II myosin Myp2. Targeting to the spindle pole body during mitosis depends on Sid4 and Cdc11, components of the septation initiation network (SIN), but not on other SIN components.
  • Stereotypical Cell Division Orientation Controls Neural Rod Midline Formation in Zebrafish
    - curr biol 20(21):1966-1972 (2010)
    The development of multicellular organisms is dependent on the tight coordination between tissue growth and morphogenesis. The stereotypical orientation of cell divisions has been proposed to be a fundamental mechanism by which proliferating and growing tissues take shape. However, the actual contribution of stereotypical division orientation (SDO) to tissue morphogenesis is unclear. In zebrafish, cell divisions with stereotypical orientation have been implicated in both body-axis elongation and neural rod formation [[1] and [2]], although there is little direct evidence for a critical function of SDO in either of these processes. Here we show that SDO is required for formation of the neural rod midline during neurulation but dispensable for elongation of the body axis during gastrulation. Our data indicate that SDO during both gastrulation and neurulation is dependent on the noncanonical Wnt receptor Frizzled 7 (Fz7) and that interfering with cell division orientation! leads to severe defects in neural rod midline formation but not body-axis elongation. These findings suggest a novel function for Fz7-controlled cell division orientation in neural rod midline formation during neurulation.
  • Believing is seeing: expectations alter visual awareness
    - curr biol 20(21):1973 (2010)

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