Monday, September 12, 2011

Hot off the presses! Sep 13 Curr Biol

The Sep 13 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:

  • New directions in crop protection
    - Curr Biol 21(17):R641-R643 (2011)
    The spread of herbicide-resistant weeds, progress in genomics, climate change and the continuing worries about pollinator decline are forcing companies to rethink their approach to crop protection. Michael Gross reports.
  • Nuptial gifts
    - Curr Biol 21(17):R644-R645 (2011)
  • Nilli Lavie
    - Curr Biol 21(17):R645-R647 (2011)
  • Paget disease of bone in a Jurassic dinosaur
    - Curr Biol 21(17):R647-R648 (2011)
    Paget disease of bone — initially described by Sir James Paget in 1876 — is a benign bone disorder well known in human pathology. It leads to the enlargement and deformity of bones due to a combination of abnormal bone resorption and abundant new bone formation [1] , [2] and [3] . There is strong evidence that viruses are involved in the disease, coupled with a probable genetic component [3] and [4] . Paget disease in humans most frequently involves the skull, the spine and parts of the pelvis [1] , [2] and [3] . There is only limited evidence on Paget disease in other extant mammals, such as orangutans and lemurs [5]. Paget disease has also been described in human bones dating back to the Neolithic [6]. Here, we report Paget disease in a vertebra of the Jurassic dinosaur Dysalotosaurus lettowvorbecki, representing the oldest indirect evidence of viruses in the fossil record.
  • The Cohesin Complex: A Platform for Checkpoint Activation and DNA Repair?
    - Curr Biol 21(17):R649-R650 (2011)
    In mitosis, the cohesin complex contributes to DNA damage checkpoint activation and repair, presumably by keeping sister chromatids linked to provide a template for repair. A recent study illustrates that this complex plays a similar role during meiosis, even though the preferred partner for meiotic DNA repair is the homologous chromosome.
  • Sensory Neurophysiology: Motion Vision during Motor Action
    - Curr Biol 21(17):R650-R652 (2011)
    A recent study identifies mechanisms of state-dependent modulation of visual processing, using a comprehensive approach of electrophysiology in the behaving animal, pharmacology and computational modelling.
  • The Circe Principle: Are Pollinators Waylaid by Attractive Habitats?
    - Curr Biol 21(17):R652-R654 (2011)
    How do pollinators move across fragmented landscapes? Attractive habitats have been viewed as facilitating pollinator movement; however, they may actually be distracting the pollinators.
  • Organelle Transport: Mitochondria Hitch a Ride on Dynamic Microtubules
    - Curr Biol 21(17):R654-R656 (2011)
    In fission yeast, microtubules control mitochondrial position by a mechanism that is dependent on microtubule dynamics but not motor proteins. A new study now reveals the molecular basis for this novel mechanism of organelle movement.
  • Sex Determination: Switch and Suppress
    - Curr Biol 21(17):R656-R659 (2011)
    The transcription factor Dmrt1 regulates male sexual development from flies and worms to humans. A newly discovered function is to suppress female differentiation in the testes. Thus, the gonadal fate decision is not final but has to be actively maintained throughout life.
  • Gene Regulation: Implications of Histone Dispersal Patterns for Epigenetics
    - Curr Biol 21(17):R659-R661 (2011)
    Histones are widely believed to carry regulatory information across cell generations. A recent study suggests limits to this model by measuring dispersal of ancestral histones in yeast.
  • Comparative Anatomy: All Vertebrates Do Have Vertebrae
    - Curr Biol 21(17):R661-R663 (2011)
    In contrast to lampreys and jawed vertebrates, hagfishes were thought to lack vertebrae. Now, long overlooked vertebral rudiments have been analysed in hagfish, suggesting that vertebrae existed in the last common ancestor of all vertebrates.
  • Subcellular Positioning: Unstable Filaments On the Move
    - Curr Biol 21(17):R663-R665 (2011)
    A key question in cell biology is how proteins and entire protein complexes localize to defined subcellular positions in non-compartmentalized cells or within cell compartments. A recent report involving computational modeling and live-cell imaging suggests that dynamically unstable protein filaments provide an adaptable and versatile positioning system.
  • Sensory Biology: Bats Feel the Air Flow
    - Curr Biol 21(17):R666-R667 (2011)
    A new study shows that hairs on the flight membranes of bats act as airflow sensors. Neurons in the brain that are sensitive to touch respond to stimulation of the hairs, and removal of the hairs compromises flight performance.
  • Uncovering New Functions for MicroRNAs in Caenorhabditis elegans
    - Curr Biol 21(17):R668-R671 (2011)
    In the nematode Caenorhabditis elegans, microRNA (miRNA) regulation of development was first observed in the striking abnormalities of lin-4 and let-7 loss of function mutants. However, after these first two miRNA mutant phenotypes were described, progress on the identification of miRNA functions in worms slowed considerably. Recent advances reveal new functions for miRNAs in embryonic and larval development as well as in the regulation of lifespan and stress response. Results from a combination of computational, biochemical, and genetic approaches have deepened our understanding of miRNA regulation of target mRNAs and support the hypothesis that miRNAs have an important role in ensuring the robustness of developmental and physiological pathways.
  • Loading of Meiotic Cohesin by SCC-2 Is Required for Early Processing of DSBs and for the DNA Damage Checkpoint
    - Curr Biol 21(17):1421-1430 (2011)
    Background Chromosome segregation and the repair of DNA double-strand breaks (DSBs) by homologous recombination require cohesin, the protein complex that mediates sister chromatid cohesion (SCC). In addition, cohesin is also required for the integrity of DNA damage checkpoints in somatic cells, where cohesin loading depends on a conserved complex containing the Scc2/Nipbl protein. Although cohesin is required for the completion of meiotic recombination, little is known about how cohesin promotes the repair of meiotic DSBs and about the factors that promote loading of cohesin during meiosis. Results Here we show that during Caenorhabditis elegans meiosis, loading of cohesin requires SCC-2, whereas the cohesin-related complexes condensin and SMC-5/6 can be loaded by mechanisms independent of both SCC-2 and cohesin. Although the lack of cohesin in scc-2 mutants impairs the repair of meiotic DSBs, surprisingly, the persistent DNA damage fails to trigger an apoptotic response of the conserved pachytene DNA damage checkpoint. Mutants carrying an scc-3 allele that abrogates loading of meiotic cohesin are also deficient in the apoptotic response of the pachytene checkpoint, and both scc-2 and scc-3 mutants fail to recruit the DNA damage sensor 9-1-1 complex onto persistent damage sites during meiosis. Furthermore, we show that meiotic cohesin is also required for the timely loading of the RAD-51 recombinase to irradiation-induced DSBs. Conclusions We propose that meiotic cohesin promotes DSB processing and recruitment of DNA damage checkpoint proteins, thus implicating cohesin in the earliest steps of the DNA damage response during meiosis.
  • mmb1p Binds Mitochondria to Dynamic Microtubules
    - Curr Biol 21(17):1431-1439 (2011)
    Background Mitochondria form a dynamic tubular network within the cell. Proper mitochondria movement and distribution are critical for their localized function in cell metabolism, growth, and survival. In mammalian cells, mechanisms of mitochondria positioning appear dependent on the microtubule cytoskeleton, with kinesin or dynein motors carrying mitochondria as cargos and distributing them throughout the microtubule network. Interestingly, the timescale of microtubule dynamics occurs in seconds, and the timescale of mitochondria distribution occurs in minutes. How does the cell couple these two time constants? Results Fission yeast also relies on microtubules for mitochondria distribution. We report here a new microtubule-dependent but motor-independent mechanism for proper mitochondria positioning in fission yeast. We identify the protein mmb1p, which binds to mitochondria and microtubules. mmb1p attaches the tubular mitochondria to the microtubule lattice at multiple discrete interaction sites. mmb1 deletion causes mitochondria to aggregate, with the long-term consequence of defective mitochondria distribution and cell death. mmb1p decreases microtubule dynamicity. Conclusions mmb1p is a new microtubule-mitochondria binding protein. We propose that mmb1p acts to couple long-term mitochondria distribution to short-term microtubule dynamics by attenuating microtubule dynamics, thus enhancing the mitochondria-microtubule interaction time.
  • Selenium Hyperaccumulators Facilitate Selenium-Tolerant Neighbors via Phytoenrichment and Reduced Herbivory
    - Curr Biol 21(17):1440-1449 (2011)
    Background Soil surrounding selenium (Se) hyperaccumulator plants was shown earlier to be enriched in Se, impairing the growth of Se-sensitive plant species. Because Se levels in neighbors of hyperaccumulators were higher and Se has been shown to protect plants from herbivory, we investigate here the potential facilitating effect of Se hyperaccumulators on Se-tolerant neighboring species in the field. Results We measured growth and herbivory of Artemisia ludoviciana and Symphyotrichum ericoides as a function of their Se concentration and proximity to hyperaccumulators Astragalus bisulcatus and Stanleya pinnata. When growing next to hyperaccumulators, A. ludoviciana and S. ericoides contained 10- to 20-fold higher Se levels (800–2,000 mg kg−1 DW) than when growing next to nonaccumulators. The roots of both species were predominantly (70%–90%) directed toward hyperaccumulator neighbors, not toward other neighbors. Moreover, neighbors of hyperaccumulators were 2-fold bigger, showed 2-fold less herbivory damage, and harbored 3- to 4-fold fewer arthropods. When used in laboratory choice and nonchoice grasshopper herbivory experiments, Se-rich neighbors of hyperaccumulators experienced less herbivory and caused higher grasshopper Se accumulation (10-fold) and mortality (4-fold). Conclusions Enhanced soil Se levels around hyperaccumulators can facilitate growth of Se-tolerant plant species through reduced herbivory and enhanced growth. This study is the first to show facilitation via enrichment with a nonessential element. It is interesting that Se enrichment of hyperaccumulator neighbors may affect competition in two ways, by reducing growth of Se-sensitive neighbors while facilitating Se-tolerant neighbors. Via these competitive and facilitating effects, Se hyperaccumulators may affect plant community composition and, consequently, higher trophic levels.
  • Distinct Roles for F-BAR Proteins Cdc15p and Bzz1p in Actin Polymerization at Sites of Endocytosis in Fission Yeast
    - Curr Biol 21(17):1450-1459 (2011)
    Background Genetic analyses of budding and fission yeast identified >50 proteins that assemble at sites of clathrin-mediated endocytosis in structures called actin patches. These proteins include clathrin, clathrin-interacting proteins, actin binding proteins, and peripheral membrane proteins such as F-BAR proteins. Many questions remain regarding the interactions of these proteins, particularly the participation of F-BAR proteins in the assembly of actin filaments. Results Our microscopic and genetic interaction experiments on fission yeast show that F-BAR proteins Cdc15p and Bzz1p accumulate in two distinct zones on invaginating membrane tubules and interact with Myo1p and Wsp1p, nucleation-promoting factors for Arp2/3 complex. The two F-BAR proteins peak prior to movement of the actin patch and their accumulation in actin patches depends on the nucleation-promoting factors. At their peak local concentrations, we estimated the stoichiometries of the proteins in actin patches to be one Bzz1p per two Wsp1p and one Cdc15p per Myo1p. Purified Bzz1p has two SH3 domains that interact with Wsp1p and stimulate actin polymerization by Arp2/3 complex. Cells lacking either Cdc15p or Bzz1p assemble 3- to 5-fold less actin in patches (in spite of normal levels of Wsp1p, Myo1p, and Arp2/3 complex), and patches move shorter distances from the plasma membrane. Conclusion We propose that during clathrin-mediated endocytosis, F-BAR proteins interact with nucleation-promoting factors to stimulate Arp2/3 complex in two different zones along the invaginating tubule. We further propose that polymerization of actin filaments in these two zones contributes to membrane scission.
  • Cortactin Controls Cell Motility and Lamellipodial Dynamics by Regulating ECM Secretion
    - Curr Biol 21(17):1460-1469 (2011)
    Background Branched actin assembly is critical for both cell motility and membrane trafficking. The branched actin regulator cortactin is generally considered to promote cell migration by controlling leading-edge lamellipodial dynamics. However, recent reports indicate that lamellipodia are not required for cell movement, suggesting an alternate mechanism. Results Because cortactin also regulates membrane trafficking and adhesion dynamics, we hypothesized that altered secretion of extracellular matrix (ECM) and/or integrin trafficking might underlie motility defects of cortactin-knockdown (KD) cells. Consistent with a primary defect in ECM secretion, both motility and lamellipodial defects of cortactin-KD cells were fully rescued by plating on increasing concentrations of exogenous ECM. Furthermore, cortactin-KD cell speed defects were rescued on cell-free autocrine ECM produced by control cells, but not on ECM produced by cortactin-KD cells. Investigation of the mechanism revealed that whereas endocytosed fibronectin (FN) is redeposited at the basal cell surface by control cells, cortactin-KD cells exhibit defective FN secretion and abnormal FN retention in a late endocytic/lysosomal compartment. Cortactin-KD motility and FN deposition defects were phenocopied by KD in control cells of the lysosomal fusion regulator synaptotagmin-7. ! Rescue of cortactin-KD cells by expression of cortactin-binding domain mutants revealed that interaction with the Arp2/3 complex and actin filaments is essential for rescue of both cell motility and autocrine ECM secretion phenotypes, whereas binding of SH3-domain partners is not required. Conclusions Efficient cell motility, promoted by cortactin regulation of branched actin networks, involves processing and resecretion of internalized ECM from a late endosomal/lysosomal compartment.
  • Preservation of the Y Transcriptome in a 10-Million-Year-Old Plant Sex Chromosome System
    - Curr Biol 21(17):1470-1474 (2011)
    Classical genetic studies discovered loss of genes from the ancient sex chromosome systems of several animals (genetic degeneration), and complete genome sequencing confirms that the heterogametic sex is hemizygous for most sex-linked genes. Genetic degeneration is thought to result from the absence of recombination between the sex chromosome pair (reviewed by [1]) and is very rapid after sex chromosome-autosome fusions in Drosophila [ [2] , [3] and [4] ]. Plant sex chromosome systems allow study of the time course of degeneration, because they evolved from a state wholly without sex chromosomes (rather than after a large genome region fused to a preexisting sex chromosome), and, in several taxa, recombination stopped very recently. However, despite increasing genetic and physical mapping of plant nonrecombining sex-determining regions [ [5] , [6] , [7] and [8] ], it remains very difficult to discover sex-linked genes, and it is unclear whether Y-linked genes ar! e losing full function. We therefore developed a high-throughput method using RNA-Seq to identify sex linkage in Silene latifolia. Recombination suppression between this plant's XY sex chromosome pair started only about 10 million years ago [9]. Our approach identifies several hundred new sex-linked genes, and we show that this young Y chromosome retains many genes, yet these already have slightly reduced gene expression and are accumulating changes likely to reduce protein functions.
  • Plant Y Chromosome Degeneration Is Retarded by Haploid Purifying Selection
    - Curr Biol 21(17):1475-1479 (2011)
    Sex chromosomes evolved many times independently in many different organisms [1]. According to the currently accepted model, X and Y chromosomes evolve from a pair of autosomes via a series of inversions leading to stepwise expansion of a nonrecombining region on the Y chromosome (NRY) and the consequential degeneration of genes trapped in the NRY [2]. Our results suggest that plants represent an exception to this rule as a result of their unique life-cycle that includes alteration of diploid and haploid generations and widespread haploid expression of genes in plant gametophytes [3]. Using a new high-throughput approach, we identified over 400 new genes expressed from X and Y chromosomes in Silene latifolia, a plant that evolved sex chromosomes about 10 million years ago. Y-linked genes show faster accumulation of amino-acid replacements and loss of expression, compared to X-linked genes. These degenerative processes are significantly less pronounced in more constrain! ed genes and genes that are likely exposed to haploid-phase selection. This may explain why plants retain hundreds of expressed Y-linked genes despite millions of years of Y chromosome degeneration, whereas animal Y chromosomes are almost completely degenerate.
  • Dscam1-Mediated Self-Avoidance Counters Netrin-Dependent Targeting of Dendrites in Drosophila
    - Curr Biol 21(17):1480-1487 (2011)
    Dendrites and axons show precise targeting and spacing patterns for proper reception and transmission of information in the nervous system. Self-avoidance promotes complete territory coverage and nonoverlapping spacing between processes from the same cell [ [1] and [2] ]. Neurons that lack Drosophila Down syndrome cell adhesion molecule 1 (Dscam1) show aberrant overlap, fasciculation, and accumulation of dendrites and axons, demonstrating a role in self-recognition and repulsion leading to self-avoidance [ [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] and [11] ]. Fasciculation and accumulation of processes suggested that Dscam1 might promote process spacing by counterbalancing developmental signals that otherwise promote self-association [ [9] and [12] ]. Here we show that Dscam1 functions to counter Drosophila sensory neuron dendritic targeting signals provided by secreted Netrin-B and Frazzled, a netrin receptor. Loss of Dscam1 function resulted in aber! rant dendrite accumulation at a Netrin-B-expressing target, whereas concomitant loss of Frazzled prevented accumulation and caused severe deficits in dendritic territory coverage. Netrin misexpression was sufficient to induce ectopic dendritic targeting in a Frazzled-dependent manner, whereas Dscam1 was required to prevent ectopic accumulation, consistent with separable roles for these receptors. Our results suggest that Dscam1-mediated self-avoidance counters extrinsic signals that are required for normal dendritic patterning, but whose action would otherwise favor neurite accumulation. Counterbalancing roles for Dscam1 may be deployed in diverse contexts during neural circuit formation.
  • The F Box Protein Partner of Paired Regulates Stability of Drosophila Centromeric Histone H3, CenH3CID
    - Curr Biol 21(17):1488-1493 (2011)
    Centromere identity and function is determined by the specific localization of CenH3 (reviewed in [ [1] , [2] , [3] , [4] , [5] , [6] and [7] ]). Several mechanisms regulate centromeric CenH3 localization, including proteasome-mediated degradation that, both in budding yeast and Drosophila, regulates CenH3 levels and prevents promiscuous misincorporation throughout chromatin [ [8] and [9] ]. CenH3CENP-A proteolysis has also been reported in senescent human cells [10] or upon infection with herpes simplex virus 1 [11]. Little is known, however, about the actual mechanisms that regulate CenH3 proteolysis. Recent work in budding yeast identified Psh1 as an E3-ubiquitin ligase that mediates degradation of CenH3Cse4p [ [12] and [13] ], but E3-ligases regulating CenH3 stability in metazoans are unknown. Here, we report that the F box protein partner of paired (Ppa), which is a variable subunit of the main E3-ligase SCF [ [14] , [15] , [16] and [17] ], mediates! CenH3CID stability in Drosophila. Our results show that Ppa depletion results in increased CenH3CID levels. Ppa physically interacts with CenH3CID through the CATDCID that, in the fly, mediates Ppa-dependent CenH3CID stability. Altogether, these results strongly suggest that, in Drosophila, SCFPpa regulates CenH3CID proteolysis. Interestingly, most known SCF complexes are inactive when, at mitosis, de novo CenH3CID deposition takes place at centromeres, suggesting that, in Drosophila, CenH3CID deposition and proteolysis are synchronized events.
  • Interhemispheric Connections Shape Subjective Experience of Bistable Motion
    - Curr Biol 21(17):1494-1499 (2011)
    The right and left visual hemifields are represented in different cerebral hemispheres and are bound together by connections through the corpus callosum. Much has been learned on the functions of these connections from split-brain patients [ [1] , [2] , [3] and [4] ], but little is known about their contribution to conscious visual perception in healthy humans. We used diffusion tensor imaging and functional magnetic resonance imaging to investigate which callosal connections contribute to the subjective experience of a visual motion stimulus that requires interhemispheric integration. The "motion quartet" is an ambiguous version of apparent motion that leads to perceptions of either horizontal or vertical motion [5]. Interestingly, observers are more likely to perceive vertical than horizontal motion when the stimulus is presented centrally in the visual field [6]. This asymmetry has been attributed to the fact that, with central fixation, perception of horizo! ntal motion requires integration across hemispheres whereas perception of vertical motion requires only intrahemispheric processing [7]. We are able to show that the microstructure of individually tracked callosal segments connecting motion-sensitive areas of the human MT/V5 complex (hMT/V5+; [8]) can predict the conscious perception of observers. Neither connections between primary visual cortex (V1) nor other surrounding callosal regions exhibit a similar relationship.
  • Kif18A Uses a Microtubule Binding Site in the Tail for Plus-End Localization and Spindle Length Regulation
    - Curr Biol 21(17):1500-1506 (2011)
    The mitotic spindle is a macromolecular structure utilized to properly align and segregate sister chromatids to two daughter cells. During mitosis, the spindle maintains a constant length, even though the spindle microtubules (MTs) are constantly undergoing polymerization and depolymerization [1]. Members of the kinesin-8 family are important for the regulation of spindle length and for chromosome positioning [ [2] , [3] , [4] , [5] , [6] , [7] , [8] and [9] ]. Kinesin-8 proteins are length-specific, plus-end-directed motors that are proposed to be either MT depolymerases [ [3] , [4] , [8] , [10] and [11] ] or MT capping proteins [12]. How Kif18A uses its destabilization activity to control spindle morphology is not known. We found that Kif18A controls spindle length independently of its role in chromosome positioning. The ability of Kif18A to control spindle length is mediated by an ATP-independent MT binding site at the C-terminal end of the Kif18A tail ! that has a strong affinity for MTs in vitro and in cells. We used computational modeling to ask how modulating the motility or binding properties of Kif18A would affect its activity. Our modeling predicts that both fast motility and a low off rate from the MT end are important for Kif18A function. In addition, our studies provide new insight into how depolymerizing and capping enzymes can lead to MT destabilization.

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