Hot off the presses! Jan 25 curr biol

The Jan 25 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:

• Social Cognition LabLinks
  - curr biol 21(2):R49-R50 (2011)
  
• Crop prices soar as climate and demand hammer markets
  - curr biol 21(2):R51-R52 (2011)
  The southern hemisphere harvest is facing problems as a new study reveals how resourceful US farmers have been over the past century and a half in growing wheat varieties to match conditions across the country. Nigel Williams reports.
• Europe challenged on GM crops
  - curr biol 21(2):R53-R54 (2011)
  The EU is under growing pressure on the GM issue. Nigel Williams reports.
• Biofuel policies under pressure
  - curr biol 21(2):R54-R55 (2011)
  The US position on biofuels is criticised but there is still optimism in future potential. Nigel Williams reports.
• Fresh swine flu worries
  - curr biol 21(2):R56-R57 (2011)
  Mediawatch: Bernard Dixon looks at how the press caught the British government by surprise by highlighting the severity of swine flu cases this winter.
• Gorilla success
  - curr biol 21(2):R57-R58 (2011)
  Think of the smallest village you know, anywhere. The chances are that it is home to more people than the entire global population of mountain gorillas, one of our closest primate relatives.
• Kevin Foster
  - curr biol 21(2):R58-R59 (2011)
  
• Aplysia
  - curr biol 21(2):R60-R61 (2011)
  
• Sexual selection
  - curr biol 21(2):R62-R65 (2011)
  Sexual selection is a concept that has probably been misunderstood and misrepresented more than any other idea in evolutionary biology, confusion that continues to the present day. We are not entirely sure why this is, but sexual politics seems to have played its role, as does a failure to understand what sexual selection is and why it was initially invoked. While in some ways less intuitive than natural selection, sexual selection is conceptually identical to it, and evolution via either mechanism will occur given sufficient genetic variation. Recent claims that sexual selection theory is fundamentally flawed are simply wrong and ignore an enormous body of evidence that provides a bedrock of support for this major mechanism of organic evolution. In fact it is partly due to this solid foundation that current research has largely shifted from documenting whether or not sexual selection occurs, to addressing more complex evolutionary questions.
• Actin-Based Motility: WAVE Regulatory Complex Structure Reopens Old SCARs
  - curr biol 21(2):R66-R68 (2011)
  The SCAR/WAVE complex controls actin polymerization at the leading edges of moving cells, but its mechanism of regulation remains unclear. The recent determination of its crystal structure, and identification of the binding sites for upstream regulators, mean its workings can finally start to be revealed.
• Protein Dynamics: Moore's Law in Molecular Biology
  - curr biol 21(2):R68-R70 (2011)
  The millisecond barrier has been broken in molecular dynamics simulations of proteins. Such simulations are increasingly revealing the inner workings of biological systems by generating atomic-level descriptions of their behaviour that make testable predictions about key molecular processes.
• Motor Memory: A Declaration of Non-Independence
  - curr biol 21(2):R70-R72 (2011)
  A new study shows that the 'fast' component of motor adaptation is distinct from its 'slow' counterpart and shares critical resources with declarative memory.
• Pyroptosis: Macrophage Suicide Exposes Hidden Invaders
  - curr biol 21(2):R72-R75 (2011)
  Caspase-1 plays a key role in host defense through its dual function in inducing a pro-inflammatory cell death termed pyroptosis and in promoting the secretion of pro-inflammatory cytokines. A new study now highlights the specific importance of pyroptosis in resistance to intracellular pathogens.
• Affective Neuroscience: Amygdala's Role in Experiencing Fear
  - curr biol 21(2):R75-R77 (2011)
  A new neuropsychological study of a rare patient provides novel evidence that amygdala lesions can virtually abolish the experience of fear, illuminating neurobiological mechanisms of fear experience.
• Microtubule Dynamics: Patronin, Protector of the Minus End
  - curr biol 21(2):R77-R79 (2011)
  It has long been surmised that cellular microtubules are capped at the minus ends to prevent their depolymerization. A recent study provides the first definitive identification of a minus-end-specific capping protein, termed Patronin, which protects the microtubule arrays of both mitotic and interphase cells.
• Neural Control: Closed-Loop Human Brain Reading
  - curr biol 21(2):R80-R81 (2011)
  Closed-loop experimental testing of single medial temporal lobe neurons in humans reveals top-down effects, opening new possibilities for describing neural representations at the highest level.
• Model Systems of Invertebrate Allorecognition
  - curr biol 21(2):R82-R92 (2011)
  Nearly all colonial marine invertebrates are capable of allorecognition — the ability to distinguish between self and genetically distinct members of the same species. When two or more colonies grow into contact, they either reject each other and compete for the contested space or fuse and form a single, chimeric colony. The specificity of this response is conferred by genetic systems that restrict fusion to self and close kin. Two selective pressures, intraspecific spatial competition between whole colonies and competition between stem cells for access to the germline in fused chimeras, are thought to drive the evolution of extensive polymorphism at invertebrate allorecognition loci. After decades of study, genes controlling allorecognition have been identified in two model systems, the protochordate Botryllus schlosseri and the cnidarian Hydractinia symbiolongicarpus. In both species, allorecognition specificity is determined by highly polymorphic cell-surface mole! cules, encoded by the fuhc and fester genes in Botryllus, and by the alr1 and alr2 genes in Hydractinia. Here we review allorecognition phenomena in both systems, summarizing recent molecular advances, comparing and contrasting the life history traits that shape the evolution of these distinct allorecognition systems, and highlighting questions that remain open in the field.
• Complexin Has Opposite Effects on Two Modes of Synaptic Vesicle Fusion
  - curr biol 21(2):97-105 (2011)
  Background Synaptic transmission can occur in a binary or graded fashion, depending on whether transmitter release is triggered by action potentials or by gradual changes in membrane potential. Molecular differences of these two types of fusion events and their differential regulation in a physiological context have yet to be addressed. Complexin is a conserved SNARE-binding protein that has been proposed to regulate both spontaneous and stimulus-evoked synaptic vesicle (SV) fusion. Results Here we examine complexin function at a graded synapse in C. elegans. Null complexin (cpx-1) mutants are viable, although nervous system function is significantly impaired. Loss of CPX-1 results in a 3-fold increase in the rate of tonic synaptic transmission at the neuromuscular junction, whereas stimulus-evoked SV fusion is decreased 10-fold. A truncated CPX-1 missing its C-terminal domain can rescue stimulus-evoked synaptic vesicle exocytosis but fails to suppress tonic activity, demonstrating that these two modes of exocytosis can be distinguished at the molecular level. A CPX-1 variant with impaired SNARE binding also rescues evoked, but not tonic, neurotransmitter release. Finally, tonic, but not evoked, release can be rescued in a syntaxin point mutant by removing CPX-1. Rescue of either form of exocytosis partially restores locomotory behavior, indicating that both types of synaptic transmission are relevant. Conclusion These observations suggest a dual role for CPX-1: suppressing SV exocytosis, driven by low levels of endogenous neural activity, while promoting synchronous fusion of SVs driven by a depolarizing stimulus. Thus, patterns of synaptic activity regulate complexin's inhibitory and permissive roles at a graded synapse.
• Complexin Maintains Vesicles in the Primed State in C. elegans
  - curr biol 21(2):106-113 (2011)
  Background Complexin binds the SNARE complex at synapses and regulates exocytosis, but genetic studies indicate contradictory roles: in flies it predominantly inhibits synaptic vesicle fusion, whereas in mice it promotes evoked responses. Results Here we characterize the complexin mutant in the nematode Caenorhabditis elegans and reveal bipolar functions in neurotransmission: complexin inhibits spontaneous fusion of synaptic vesicles but is also essential for evoked responses. Complexin mutants exhibit a doubling of vesicle fusion in the absence of extracellular calcium. Even more profoundly, mutants exhibit an almost complete loss of evoked responses, and current amplitudes are reduced by 94%. One possible interpretation is that complexin is required for the stabilization of docked vesicles and that, in its absence, vesicles may fuse or undock from the plasma membrane. Consistent with this hypothesis, docked synaptic vesicles are reduced by 70% in complexin-1 mutants. Conclusion These data suggest that the main function of complexin is to maintain the docked state both by inhibiting fusion and by promoting priming.
• A Secreted Protein Promotes Cleavage Furrow Maturation during Cytokinesis
  - curr biol 21(2):114-119 (2011)
  Developmental modifications in cell shape depend on dynamic interactions between the extracellular matrix and cytoskeleton. In contrast, existing models of cytokinesis describe substantial cell surface remodeling that involves many intracellular regulatory and structural proteins but includes no contribution from the extracellular matrix [[1], [2] and [3]]. Here, we show that extracellular hemicentins assemble at the cleavage furrow of dividing cells in the C. elegans germline and in preimplantation mouse embryos. In the absence of hemicentin, cleavage furrows form but retract prior to completion, resulting in multinucleate cells. In addition to their role in tissue organization, the data indicate that hemicentins are the first secreted proteins required during mammalian development and the only known secreted proteins required for cytokinesis, with an evolutionarily conserved role in stabilizing and preventing retraction of nascent cleavage furrows. Together with stud! ies showing that extracellular polysaccharides are required for cytokinesis in diverse species [[4], [5], [6], [7], [8] and [9]], our data suggest that assembly of a cell type-specific extracellular matrix may be a general requirement for cleavage furrow maturation and contractile ring function during cytokinesis.
• Temporal Repression of Core Circadian Genes Is Mediated through EARLY FLOWERING 3 in Arabidopsis
  - curr biol 21(2):120-125 (2011)
  The circadian clock provides robust, 24 hr biological rhythms throughout the eukaryotes. The clock gene circuit in plants comprises interlocking transcriptional feedback loops, reviewed in [1], whereby the morning-expressed transcription factors CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY) repress the expression of evening genes, notably TIMING OF CAB EXPRESSION 1 (TOC1). EARLY FLOWERING 3 (ELF3) has been implicated as a repressor of light signaling to the clock [[2] and [3]] and, paradoxically, as an activator of the light-induced genes CCA1 and LHY [[4] and [5]]. We use cca1-11 lhy-21 elf3-4 plants to separate the repressive function of ELF3 from its downstream targets CCA1 and LHY. We further demonstrate that ELF3 associates physically with the promoter of PSEUDO-RESPONSE REGULATOR 9 (PRR9), a repressor of CCA1 and LHY expression, in a time-dependent fashion. The repressive function of ELF3 is thus consistent with indirect activation of LHY! and CCA1, in a double-negative connection via a direct ELF3 target, PRR9. This mechanism reconciles the functions of ELF3 in the clock network during the night and points to further effects of ELF3 during the day.
• LUX ARRHYTHMO Encodes a Nighttime Repressor of Circadian Gene Expression in the Arabidopsis Core Clock
  - curr biol 21(2):126-133 (2011)
  Circadian clocks provide an adaptive advantage by allowing organisms to anticipate daily and seasonal environmental changes [[1] and [2]]. Eukaryotic oscillators rely on complex hierarchical networks composed of transcriptional and posttranslational regulatory circuits [3]. In Arabidopsis, current representations of the circadian clock consist of three or four interlocked transcriptional feedback loops [[3] and [4]]. Although molecular components contributing to different domains of these circuits have been described, how the loops are connected at the molecular level is not fully understood. Genetic screens previously identified LUX ARRHYTHMO (LUX) [5], also known as PHYTOCLOCK1 (PCL1) [6], an evening-expressed putative transcription factor essential for circadian rhythmicity. We determined the in vitro DNA-binding specificity for LUX by using universal protein binding microarrays; we then demonstrated that LUX directly regulates the expression of PSEUDO RESPONSE REGU! LATOR9 (PRR9), a major component of the morning transcriptional feedback circuit, through association with the newly discovered DNA binding site. We also show that LUX binds to its own promoter, defining a new negative autoregulatory feedback loop within the core clock. These novel connections between the archetypal loops of the Arabidopsis clock represent a significant advance toward defining the molecular dynamics underlying the circadian network in plants and provide the first mechanistic insight into the molecular function of the previously orphan clock factor LUX.
• Horizontal Transfer of a Large and Highly Toxic Secondary Metabolic Gene Cluster between Fungi
  - curr biol 21(2):134-139 (2011)
  Genes involved in intermediary and secondary metabolism in fungi are frequently physically linked or clustered. For example, in Aspergillus nidulans the entire pathway for the production of sterigmatocystin (ST), a highly toxic secondary metabolite and a precursor to the aflatoxins (AF), is located in a 54 kb, 23 gene cluster. We discovered that a complete ST gene cluster in Podospora anserina was horizontally transferred from Aspergillus. Phylogenetic analysis shows that most Podospora cluster genes are adjacent to or nested within Aspergillus cluster genes, although the two genera belong to different taxonomic classes. Furthermore, the Podospora cluster is highly conserved in content, sequence, and microsynteny with the Aspergillus ST/AF clusters and its intergenic regions contain 14 putative binding sites for AflR, the transcription factor required for activation of the ST/AF biosynthetic genes. Examination of 52,000 Podospora expressed sequence tags identified tran! scripts for 14 genes in the cluster, with several expressed at multiple life cycle stages. The presence of putative AflR-binding sites and the expression evidence for several cluster genes, coupled with the recent independent discovery of ST production in Podospora [1], suggest that this HGT event probably resulted in a functional cluster. Given the abundance of metabolic gene clusters in fungi, our finding that one of the largest known metabolic gene clusters moved intact between species suggests that such transfers might have significantly contributed to fungal metabolic diversity. PaperFlick To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon below Download this Video (23212 K)
• Motion Silences Awareness of Visual Change
  - curr biol 21(2):140-143 (2011)
  Loud bangs, bright flashes, and intense shocks capture attention, but other changes—even those of similar magnitude—can go unnoticed. Demonstrations of change blindness have shown that observers fail to detect substantial alterations to a scene when distracted by an irrelevant flash, or when the alterations happen gradually [[1], [2], [3], [4] and [5]]. Here, we show that objects changing in hue, luminance, size, or shape appear to stop changing when they move. This motion-induced failure to detect change, silencing, persists even though the observer attends to the objects, knows that they are changing, and can make veridical judgments about their current state. Silencing demonstrates the tight coupling of motion and object appearance.
• View-Based Encoding of Actions in Mirror Neurons of Area F5 in Macaque Premotor Cortex
  - curr biol 21(2):144-148 (2011)
  Converging experimental evidence indicates that mirror neurons in the monkey premotor area F5 encode the goals of observed motor acts [[1], [2] and [3]]. However, it is unknown whether they also contribute to encoding the perspective from which the motor acts of others are seen. In order to address this issue, we recorded the visual responses of mirror neurons of monkey area F5 by using a novel experimental paradigm based on the presentation of movies showing grasping motor acts from different visual perspectives. We found that the majority of the tested mirror neurons (74%) exhibited view-dependent activity with responses tuned to specific points of view. A minority of the tested mirror neurons (26%) exhibited view-independent responses. We conclude that view-independent mirror neurons encode action goals irrespective of the details of the observed motor acts, whereas the view-dependent ones might either form an intermediate step in the formation of view independence ! or contribute to a modulation of view-dependent representations in higher-level visual areas, potentially linking the goals of observed motor acts with their pictorial aspects.
• Opsin Is a Phospholipid Flippase
  - curr biol 21(2):149-153 (2011)
  Polar lipids must flip-flop rapidly across biological membranes to sustain cellular life [[1] and [2]], but flipping is energetically costly [3] and its intrinsic rate is low. To overcome this problem, cells have membrane proteins that function as lipid transporters (flippases) to accelerate flipping to a physiologically relevant rate. Flippases that operate at the plasma membrane of eukaryotes, coupling ATP hydrolysis to unidirectional lipid flipping, have been defined at a molecular level [2]. On the other hand, ATP-independent bidirectional flippases that translocate lipids in biogenic compartments, e.g., the endoplasmic reticulum, and specialized membranes, e.g., photoreceptor discs [[4] and [5]], have not been identified even though their activity has been recognized for more than 30 years [1]. Here, we demonstrate that opsin is the ATP-independent phospholipid flippase of photoreceptor discs. We show that reconstitution of opsin into large unilamellar vesicles pr! omotes rapid (τ < 10 s) flipping of phospholipid probes across the vesicle membrane. This is the first molecular identification of an ATP-independent phospholipid flippase in any system. It reveals an unexpected activity for opsin and, in conjunction with recently available structural information on this G protein-coupled receptor [[6] and [7]], significantly advances our understanding of the mechanism of ATP-independent lipid flip-flop.
• A Nonmotor Microtubule Binding Site in Kinesin-5 Is Required for Filament Crosslinking and Sliding
  - curr biol 21(2):154-160 (2011)
  Kinesin-5, a widely conserved motor protein required for assembly of the bipolar mitotic spindle in eukaryotes, forms homotetramers with two pairs of motor domains positioned at opposite ends of a dumbbell-shaped molecule [[1], [2] and [3]]. It has long been assumed that this configuration of motor domains is the basis of kinesin-5's ability to drive relative sliding of microtubules [[2], [4] and [5]]. Recently, it was suggested that in addition to the N-terminal motor domain, kinesin-5 also has a nonmotor microtubule binding site in its C terminus [6]. However, it is not known how the nonmotor domain contributes to motor activity, or how a kinesin-5 tetramer utilizes a combination of four motor and four nonmotor microtubule binding sites for its microtubule organizing functions. Here we show, in single molecule assays, that kinesin-5 homotetramers require the nonmotor C terminus for crosslinking and relative sliding of two microtubules. Remarkably, this domain enhance! s kinesin-5's microtubule binding without substantially reducing motor activity. Our results suggest that tetramerization of kinesin-5's low-processivity motor domains is not sufficient for microtubule sliding because the motor domains alone are unlikely to maintain persistent microtubule crosslinks. Rather, kinesin-5 utilizes nonmotor microtubule binding sites to tune its microtubule attachment dynamics, enabling it to efficiently align and sort microtubules during metaphase spindle assembly and function.
• Transcriptional Profiling Identifies TNS4 Function in Epithelial Tubulogenesis
  - curr biol 21(2):161-166 (2011)
  Hepatocyte growth factor (HGF) plays central roles in tubulogenesis and metastasis [[1], [2], [3] and [4]]. HGF treatment of Madin-Darby canine kidney (MDCK) cells grown as cysts in three-dimensional culture induces tubulogenesis [[5] and [6]], which like most tubulogenic processes proceeds through distinct intermediate phases. Identification of genes associated with these phases is central to understanding the molecular mechanisms of tubulogensis; however, because of inefficient, asynchronous tubule formation, isolating such genes has been unfeasible. Here we developed a synchronous, efficient tubulogenesis system and used time-course transcriptional profiling to identify genes temporally regulated in developmental intermediates. Knockdown (KD) of tensin 4 (TNS4), a particularly highly upregulated gene, leads to a decrease in formation of extensions and tubules, two sequential intermediates in tubulogenesis. Exogenous expression of TNS4 marks invasive cells in an epit! helial sheet. A mutation in the SH2 domain of TNS4 prevents the transition from extension formation to invasive migration during tubule formation and leads to increased basal activation of STAT3. Exogenous expression of a constitutively active STAT3 mimics the defect by the mutation. Our study highlights the role of the TNS4-STAT3 axis in epithelial sheet invasion and tubulogenesis.
• Regulation of Stereocilia Length by Myosin XVa and Whirlin Depends on the Actin-Regulatory Protein Eps8
  - curr biol 21(2):167-172 (2011)
  Myosin XVa (MyoXVa) and its cargo whirlin are implicated in deafness and vestibular dysfunction and have been shown to localize at stereocilia tips and to be essential for the elongation of these actin protrusions [[1], [2], [3] and [4]]. Given that whirlin has no known actin-regulatory activity, it remains unclear how these proteins work together to influence stereocilia length. Here we show that the actin-regulatory protein Eps8 [5] interacts with MyoXVa and that mice lacking Eps8 show short stereocilia compared to MyoXVa- and whirlin-deficient mice. We show that Eps8 fails to accumulate at the tips of stereocilia in the absence of MyoXVa, that overexpression of MyoXVa results in both elongation of stereocilia and increased accumulation of Eps8 at stereocilia tips, and that the exogenous expression of MyoXVa in MyoXVa-deficient hair cells rescues Eps8 tip localization. We find that Eps8 also interacts with whirlin and that the expression of both Eps8 and MyoXVa at st! ereocilia tips is reduced in whirlin-deficient mice. We conclude that MyoXVa, whirlin, and Eps8 are integral components of the stereocilia tip complex, where Eps8 is a central actin-regulatory element for elongation of the stereocilia actin core.